Differential introgression and the maintenance of species boundaries in an advanced generation avian hybrid zone

Background: Evolutionary processes, including selection and differential fitness, shape the introgression of genetic material across a hybrid zone, resulting in the exchange of some genes but not others. Differential introgression of molecular or phenotypic markers can thus provide insight into factors contributing to reproductive isolation. We characterized patterns of genetic variation across a hybrid zone between two tidal marsh birds, Saltmarsh (Ammodramus caudacutus) and Nelson’s (A. nelsoni) sparrows (n = 286), and compared patterns of introgression among multiple genetic markers and phenotypic traits. Results: Geographic and genomic cline analyses revealed variable patterns of introgression among marker types. Most markers exhibited gradual clines and indicated that introgression exceeds the spatial extent of the previously documented hybrid zone. We found steeper clines, indicating strong selection for loci associated with traits related to tidal marsh adaptations, including for a marker linked to a gene region associated with metabolic functions, including an osmotic regulatory pathway, as well as for a marker related to melanin-based pigmentation, supporting an adaptive role of darker plumage (salt marsh melanism) in tidal marshes. Narrow clines at mitochondrial and sex-linked markers also offer support for Haldane’s rule. We detected patterns of asymmetrical introgression toward A. caudacutus, which may be driven by differences in mating strategy or differences in population density between the two species. Conclusions: Our findings offer insight into the dynamics of a hybrid zone traversing a unique environmental gradient and provide evidence for a role of ecological divergence in the maintenance of pure species boundaries despite ongoing gene flow

Differential introgression and the maintenance of species boundaries in an advanced generation avian hybrid zone

Background: Evolutionary processes, including selection and differential fitness, shape the introgression of genetic material across a hybrid zone, resulting in the exchange of some genes but not others. Differential introgression of molecular or phenotypic markers can thus provide insight into factors contributing to reproductive isolation. We characterized patterns of genetic variation across a hybrid zone between two tidal marsh birds, Saltmarsh (Ammodramus caudacutus) and Nelson’s (A. nelsoni) sparrows (n = 286), and compared patterns of introgression among multiple genetic markers and phenotypic traits. Results: Geographic and genomic cline analyses revealed variable patterns of introgression among marker types. Most markers exhibited gradual clines and indicated that introgression exceeds the spatial extent of the previously documented hybrid zone. We found steeper clines, indicating strong selection for loci associated with traits related to tidal marsh adaptations, including for a marker linked to a gene region associated with metabolic functions, including an osmotic regulatory pathway, as well as for a marker related to melanin-based pigmentation, supporting an adaptive role of darker plumage (salt marsh melanism) in tidal marshes. Narrow clines at mitochondrial and sex-linked markers also offer support for Haldane’s rule. We detected patterns of asymmetrical introgression toward A. caudacutus, which may be driven by differences in mating strategy or differences in population density between the two species. Conclusions: Our findings offer insight into the dynamics of a hybrid zone traversing a unique environmental gradient and provide evidence for a role of ecological divergence in the maintenance of pure species boundaries despite ongoing gene flow

Genotype-environment associations support a mosaic hybrid zone between two tidal marsh birds

Local environmental features can shape hybrid zone dynamics when hybrids are bounded by ecotones or when patchily distributed habitat types lead to a corresponding mosaic of genotypes. We investigated the role of marsh-level characteristics in shaping a hybrid zone between two recently diverged avian taxa – Saltmarsh (Ammodramus caudacutus) and Nelson\u27s (A. nelsoni) sparrows. These species occupy different niches where allopatric, with caudacutus restricted to coastal marshes and nelsoni found in a broader array of wetland and grassland habitats and co-occur in tidal marshes in sympatry. We determined the influence of habitat types on the distribution of pure and hybrid sparrows and assessed the degree of overlap in the ecological niche of each taxon. To do this, we sampled and genotyped 305 sparrows from 34 marshes across the hybrid zone and from adjacent regions. We used linear regression to test for associations between marsh characteristics and the distribution of pure and admixed sparrows. We found a positive correlation between genotype and environmental variables with a patchy distribution of genotypes and habitats across the hybrid zone. Ecological niche models suggest that the hybrid niche was more similar to that of A. nelsoni and habitat suitability was influenced strongly by distance from coastline. Our results support a mosaic model of hybrid zone maintenance, suggesting a role for local environmental features in shaping the distribution and frequency of pure species and hybrids across space

Genotype-environment associations support a mosaic hybrid zone between two tidal marsh birds

Local environmental features can shape hybrid zone dynamics when hybrids are bounded by ecotones or when patchily distributed habitat types lead to a corresponding mosaic of genotypes. We investigated the role of marsh-level characteristics in shaping a hybrid zone between two recently diverged avian taxa – Saltmarsh (Ammodramus caudacutus) and Nelson\u27s (A. nelsoni) sparrows. These species occupy different niches where allopatric, with caudacutus restricted to coastal marshes and nelsoni found in a broader array of wetland and grassland habitats and co-occur in tidal marshes in sympatry. We determined the influence of habitat types on the distribution of pure and hybrid sparrows and assessed the degree of overlap in the ecological niche of each taxon. To do this, we sampled and genotyped 305 sparrows from 34 marshes across the hybrid zone and from adjacent regions. We used linear regression to test for associations between marsh characteristics and the distribution of pure and admixed sparrows. We found a positive correlation between genotype and environmental variables with a patchy distribution of genotypes and habitats across the hybrid zone. Ecological niche models suggest that the hybrid niche was more similar to that of A. nelsoni and habitat suitability was influenced strongly by distance from coastline. Our results support a mosaic model of hybrid zone maintenance, suggesting a role for local environmental features in shaping the distribution and frequency of pure species and hybrids across space

Fine-scale population structure and asymmetrical dispersal in an obligate salt-marsh passerine, the Saltmarsh Sparrow (Ammodramus Caudacutus)

Understanding the spatial scale of gene flow can yield valuable insight into the ecology of an organism and guide conservation strategies. Fine-scale genetic structure is uncommon in migratory passerines because of their high vagility and presumed high dispersal abilities. Aspects of the behavior and ecology of some migratory species, however, may promote structure on a finer scale in comparison to their mobility. We investigated population genetic structure in the Saltmarsh Sparrow (Ammodramus caudacutus), a migratory passerine that breeds along the northeastern coast of the United States, where it is restricted exclusively to a narrow strip of patchily distributed tidal marsh habitat. Using genotyping with 10 microsatellite loci, we detected weak but significant population structure among Saltmarsh Sparrows from nine marshes on the breeding grounds between Scarborough, Maine, and Oceanside, New York. Genetic variation among marshes was largely consistent with a pattern of isolation by distance, with some exceptions. One inland marsh was genetically divergent despite its proximity to other sampled marshes, which suggests that mechanisms besides geographic distance influence population genetic structure. Bayesian clustering, multivariate analyses, and assignment tests supported a population structure consisting of five groups. Estimates of migration rates indicated variation in gene flow among marshes, which suggests asymmetrical dispersal and possible source-sink population dynamics. The genetic structure that we found in Saltmarsh Sparrows may result from natal philopatry and breeding-site fidelity, combined with restricted dispersal due to obligate dependence on a patchy habitat. Our findings suggest that fine-scale population structure may be important in some migratory passerines. Received 12 July 2011, accepted 1 February 2012

Relationship of phenotypic variation and genetic admixture in the Saltmarsh–Nelson\u27s sparrow hybrid zone

Hybridization is influential in shaping species\u27 dynamics and has many evolutionary and conservation implications. Identification of hybrid individuals typically relies on morphological data, but the assumption that hybrids express intermediate traits is not always valid, because of complex patterns of introgression and selection. We characterized phenotypic and genotypic variation across a hybrid zone between 2 tidal-marsh birds, the Saltmarsh Sparrow (Ammodramus caudacutus) and Nelson\u27s Sparrow (A. nelsoni) (n = 290), and we sought to identify morphological traits that could be used to classify admixed individuals. Sparrows were sampled from a total of 34 marshes, including 23 sympatric and 11 putatively allopatric marshes. Each individual was scored at 13 plumage traits, and standard morphometric data were collected. We used genotyping analysis at 24 microsatellite loci to categorize individuals into genotypic classes of pure, F1–F2, or backcrossed. Genetic data revealed that 52% of individuals sampled along the geographic transect were of mixed ancestry, and the majority of these were backcrossed. Traits related to the definition of plumage features (streaking, crown, and face) showed less overlap between genotypic classes than traits related to the amount or color of plumage features. Although morphological data performed well in distinguishing between the 2 taxa, pure and backcrossed individuals of each parental type could not be distinguished because of substantial overlap in plumage and morphology. We conclude that the discrimination of pure and hybrid individuals is not possible in the absence of genetic data. Our results have implications for conservation of pure populations, as extensive backcrossing throughout the hybrid zone may present challenges for monitoring pure species identified by morphology alone

Correlation of Formative Assessments as the Means of Predicting Summative Performance in Paramedic Students

Background: Paramedic programs use formative assessments to determine cognitive competency. Understanding the number of failed units as a probability of passing the summative exam will allow programs to set additional benchmarks. The purpose of this study was to determine whether failure in formative exams determines success on a summative exam. Methods: Formative and summative scores from 2011 - 2016 for paramedic students with accounts in Fisdap, an Internet-based administrative database, were retrospectively reviewed for the following criteria: provided consent for research, completed all six formative (unit) examinations, and completed a summative (comprehensive) examination. Analyses were performed with Pearson correlations and linear regression. Results: A total of 1,406 student records were included based on inclusion criteria. Correlation with each formative and the summative examination were all significant, p \u3c0.001: Cardiology 0.597; Airway 0.571; Medical 0.571; Trauma 0.566; Ob/Pediatrics 0.549; Operations 0.495. The cardiology exam was shown to have a moderate correlation on summative performance, whereas the operations exam had the weakest correlation. The number of formative examination failures was a significant predictor of the probability of passing the summative examination, t(1405) - -31.02 p\u3c0.001. Zero failed unit examinations yielded a 100% probability of passing. Three failed formative exams yielded a 60.4% probability. Four failed attempts yielded a 44.8% probability. Failure of all six formative exams yielded a 13.4% probability of passing the Paramedic Readiness Exam Version 3. Conclusion: Not all formative examinations hold the same predictive power on the probability of passing a summative examination. Each had their own correlation value. Students who did not fail formative examinations have a 100% likelihood of passing the summative examination

Gabapentin Drug Misuse Signals: A Pharmacovigilance Assessment Using the FDA Adverse Event Reporting System

Background: Although there have been increasing reports of intentional gabapentin misuse, epidemiological evidence for the phenomenon is limited. The purpose of this study was to determine whether there are pharmacovigilance abuse signals for gabapentin.Methods: Using FDA Adverse Events Reporting System reports from January 1, 2005 to December 31, 2015, we calculated pharmacovigilance signal measures (i.e., reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean) for abuse-related adverse event (AR-AE)-gabapentin pairs. Loglinear modeling assessed the frequency of concurrent reporting of abuse-related and abusespecific AEs (AS-AEs) associated with gabapentin. Findings were compared to a positive (pregabalin) and negative (duloxetine) control.Results: From 2005-2015 there were 5,951,229 unique AE reports submitted to the FDA including 99,977 for gabapentin, 73,977 for duloxetine, and 97,813 for pregabalin. Significant drug-AR-AE pair signals involving gabapentin included: drug abuser, multiple drug overdose, and substance-induced psychotic disorder. Significant drug AR-AE signals involving gabapentin and pregabalin, but not duloxetine, were: ataxia, dependence, drug abuse, increased drug tolerance, and overdose. Compared to duloxetine, gabapentin had significantly greater odds of a coreport for an AS-AE with drug withdrawal syndrome (OR: 6.55), auditory hallucinations (OR: 4.57), delusions (OR: 2.36), euphoric mood (OR: 5.45), ataxia (OR: 2.85), drug abuser (OR: 3.01), aggression (OR: L98), psychotic disorder (OR: 1.96), and feeling abnormal (OR: 1.31).Conclusions: We identified abuse-related signals for gabapentin and highlighted several CNS effects that may be associated with its abuse. Gabapentin prescribers should be aware of the drug\u27s abuse liability and effects that may accompany its use

Membrane integrity contributes to resistance of Cryptococcus neoformans to the cell wall inhibitor caspofungin

The fungal pathogen Cryptococcus neoformans causes up to 278 000 infections each year globally, resulting in up to 180,000 deaths annually, mostly impacting immunocompromised people. Therapeutic options for C. neoformans infections are very limited. Caspofungin, a member of the echinocandin class of antifungals, is generally well tolerated but clinically ineffective against C. neoformans. We sought to identify biological processes that can be targeted to render the cell more susceptible to echinocandins by screening the available libraries of gene deletion mutants made in the KN99α background for caspofungin sensitivity. We adapted a Candida albicans fungal biofilm assay for the growth characteristics of C. neoformans and systematically screened 4,030 individual gene deletion mutants in triplicate plate assays. We identified 25 strains that showed caspofungin sensitivity. We followed up with a dose dependence assay, and 17 of the 25 were confirmed sensitive, 5 of which were also sensitive in an agar plate assay. We made new deletion mutant strains for four of these genes