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1.
Mol Ecol ; 29(17): 3217-3233, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682353

RESUMO

Genetic structure in host species is often used to predict disease spread. However, host and pathogen genetic variation may be incongruent. Understanding landscape factors that have either concordant or divergent influence on host and pathogen genetic structure is crucial for wildlife disease management. Devil facial tumour disease (DFTD) was first observed in 1996 and has spread throughout almost the entire Tasmanian devil geographic range, causing dramatic population declines. Whereas DFTD is predominantly spread via biting among adults, devils typically disperse as juveniles, which experience low DFTD prevalence. Thus, we predicted little association between devil and tumour population structure and that environmental factors influencing gene flow differ between devils and tumours. We employed a comparative landscape genetics framework to test the influence of environmental factors on patterns of isolation by resistance (IBR) and isolation by environment (IBE) in devils and DFTD. Although we found evidence for broad-scale costructuring between devils and tumours, we found no relationship between host and tumour individual genetic distances. Further, the factors driving the spatial distribution of genetic variation differed for each. Devils exhibited a strong IBR pattern driven by major roads, with no evidence of IBE. By contrast, tumours showed little evidence for IBR and a weak IBE pattern with respect to elevation in one of two tumour clusters we identify herein. Our results warrant caution when inferring pathogen spread using host population genetic structure and suggest that reliance on environmental barriers to host connectivity may be ineffective for managing the spread of wildlife diseases. Our findings demonstrate the utility of comparative landscape genetics for identifying differential factors driving host dispersal and pathogen transmission.

2.
AAPS PharmSciTech ; 21(5): 185, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632542

RESUMO

The present study aimed to develop, characterize and evaluate the amphotericin B-loaded nanostructured lipid carriers (AmB-NLCs) for topical treatment of cutaneous leishmaniasis (CL) and vulvovaginal candidiasis (VVC). AmB-NLCs were characterized for particle size, zeta potential, encapsulation efficiency and surface morphology. Prepared NLCs were also characterized for in vitro drug release, ex vivo skin permeation and deposition before evaluating their in vitro and in vivo efficacy. Cytotoxicity of NLCs was assessed on MRC-5 cells, whereas skin irritation potential was evaluated in vivo using rats. Significant accumulation of drug in to the skin supported the topical application potential of drug-loaded NLCs. Encapsulation of AmB in NLCs resulted in enhanced in vitro potency against promastigotes and intracellular amastigotes of L. major JISH 118 (IC50 ± SEM = 0.02 ± 0.1 µM for both) compared with free drug (IC50 ± SEM = 0.15 ± 0.2 & 0.14 ± 0.0, respectively). Similar improved potency of AmB-NLCs was also observed for other Leishmania and fungal strains compared with drug solution. Topical application of AmB-NLCs on L. major-infected BALB/c mice caused a significant reduction in parasite burden per mg of lesion (65 × 108 ± 13) compared with the control group (> 167.8 × 108 ± 11). Topical AmB-NLCs gel demonstrated superior efficacy in the vaginal C. albicans rat model for VVC as compared with plain AmB gel. Moreover, results of in vitro cytotoxicity assay and in vivo skin irritation test confirmed AmB-NLCs to be non-toxic and safe for topical use. In conclusion, NLCs may have promising potential as carrier for topical treatment of various conditions of skin and mucosa.


Assuntos
Anfotericina B/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Nanoestruturas/administração & dosagem , Administração Tópica , Animais , Candidíase Vulvovaginal/metabolismo , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Géis/metabolismo , Humanos , Lipídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Tamanho da Partícula , Ratos , Pele/metabolismo , Absorção Cutânea
3.
Evolution ; 74(7): 1392-1408, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32445281

RESUMO

Landscape genomics studies focus on identifying candidate genes under selection via spatial variation in abiotic environmental variables, but rarely by biotic factors (i.e., disease). The Tasmanian devil (Sarcophilus harrisii) is found only on the environmentally heterogeneous island of Tasmania and is threatened with extinction by a transmissible cancer, devil facial tumor disease (DFTD). Devils persist in regions of long-term infection despite epidemiological model predictions of species' extinction, suggesting possible adaptation to DFTD. Here, we test the extent to which spatial variation and genetic diversity are associated with the abiotic environment (i.e., climatic variables, elevation, vegetation cover) and/or DFTD. We employ genetic-environment association analyses using 6886 SNPs from 3287 individuals sampled pre- and post-disease arrival across the devil's geographic range. Pre-disease, we find significant correlations of allele frequencies with environmental variables, including 365 unique loci linked to 71 genes, suggesting local adaptation to abiotic environment. The majority of candidate loci detected pre-DFTD are not detected post-DFTD arrival. Several post-DFTD candidate loci are associated with disease prevalence and were in linkage disequilibrium with genes involved in tumor suppression and immune response. Loss of apparent signal of abiotic local adaptation post-disease suggests swamping by strong selection resulting from the rapid onset of DFTD.

4.
Mol Biol Evol ; 36(12): 2906-2921, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424552

RESUMO

Reconstructing species' demographic histories is a central focus of molecular ecology and evolution. Recently, an expanding suite of methods leveraging either the sequentially Markovian coalescent (SMC) or the site-frequency spectrum has been developed to reconstruct population size histories from genomic sequence data. However, few studies have investigated the robustness of these methods to genome assemblies of varying quality. In this study, we first present an improved genome assembly for the Tasmanian devil using the Chicago library method. Compared with the original reference genome, our new assembly reduces the number of scaffolds (from 35,975 to 10,010) and increases the scaffold N90 (from 0.101 to 2.164 Mb). Second, we assess the performance of four contemporary genomic methods for inferring population size history (PSMC, MSMC, SMC++, Stairway Plot), using the two devil genome assemblies as well as simulated, artificially fragmented genomes that approximate the hypothesized demographic history of Tasmanian devils. We demonstrate that each method is robust to assembly quality, producing similar estimates of Ne when simulated genomes were fragmented into up to 5,000 scaffolds. Overall, methods reliant on the SMC are most reliable between ∼300 generations before present (gbp) and 100 kgbp, whereas methods exclusively reliant on the site-frequency spectrum are most reliable between the present and 30 gbp. Our results suggest that when used in concert, genomic methods for reconstructing species' effective population size histories 1) can be applied to nonmodel organisms without highly contiguous reference genomes, and 2) are capable of detecting independently documented effects of historical geological events.


Assuntos
Demografia/métodos , Genoma , Genômica/métodos , Genômica/normas , Marsupiais/genética , Animais , Feminino
5.
Sci Rep ; 9(1): 10130, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300735

RESUMO

Although population viability analysis (PVA) can be an important tool for strengthening endangered species recovery efforts, the extent to which such analyses remain embedded in the social process of recovery planning is often unrecognized. We analyzed two recovery plans for the Mexican wolf that were developed using similar data and methods but arrived at contrasting conclusions as to appropriate recovery goals or criteria. We found that approximately half of the contrast arose from uncertainty regarding biological data, with the remainder divided between policy-related decisions and mixed biological-policy factors. Contrasts arose from both differences in input parameter values and how parameter uncertainty informed the level of precaution embodied in resulting criteria. Policy-related uncertainty originated from contrasts in thresholds for acceptable risk and disagreement as to how to define endangered species recovery. Rather than turning to PVA to produce politically acceptable definitions of recovery that appear science-based, agencies should clarify the nexus between science and policy elements in their decision processes. The limitations we identify in endangered-species policy and how PVAs are conducted as part of recovery planning must be addressed if PVAs are to fulfill their potential to increase the odds of successful conservation outcomes.

6.
Heredity (Edinb) ; 122(2): 133-149, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29880893

RESUMO

Admixture resulting from natural dispersal processes can potentially generate novel phenotypic variation that may facilitate persistence in changing environments or result in the loss of population-specific adaptations. Yet, under the US Endangered Species Act, policy is limited for management of individuals whose ancestry includes a protected taxon; therefore, they are generally not protected under the Act. This issue is exemplified by the recently re-established grey wolves of the Pacific Northwest states of Washington and Oregon, USA. This population was likely founded by two phenotypically and genetically distinct wolf ecotypes: Northern Rocky Mountain (NRM) forest and coastal rainforest. The latter is considered potentially threatened in southeast Alaska and thus the source of migrants may affect plans for their protection. To assess the genetic source of the re-established population, we sequenced a ~ 300 bp portion of the mitochondrial control region and ~ 5 Mbp of the nuclear genome. Genetic analysis revealed that the Washington wolves share ancestry with both wolf ecotypes, whereas the Oregon population shares ancestry with NRM forest wolves only. Using ecological niche modelling, we found that the Pacific Northwest states contain environments suitable for each ecotype, with wolf packs established in both environmental types. Continued migration from coastal rainforest and NRM forest source populations may increase the genetic diversity of the Pacific Northwest population. However, this admixed population challenges traditional management regimes given that admixture occurs between an adaptively distinct ecotype and a more abundant reintroduced interior form. Our results emphasize the need for a more precise US policy to address the general problem of admixture in the management of endangered species, subspecies, and distinct population segments.


Assuntos
Espécies em Perigo de Extinção , Lobos/crescimento & desenvolvimento , Distribuição Animal , Animais , Cruzamento , Conservação dos Recursos Naturais , Ecossistema , Espécies em Perigo de Extinção/estatística & dados numéricos , Feminino , Genótipo , Masculino , Noroeste dos Estados Unidos , Dinâmica Populacional , Lobos/classificação , Lobos/genética , Lobos/fisiologia
7.
Genome Biol Evol ; 10(11): 3012-3025, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30321343

RESUMO

Understanding the genetic basis of disease-related phenotypes, such as cancer susceptibility, is crucial for the advancement of personalized medicine. Although most cancers are somatic in origin, a small number of transmissible cancers have been documented. Two such cancers have emerged in the Tasmanian devil (Sarcophilus harrisii) and now threaten the species with extinction. Recently, cases of natural tumor regression in Tasmanian devils infected with the clonally contagious cancer have been detected. We used whole-genome sequencing and FST-based approaches to identify the genetic basis of tumor regression by comparing the genomes of seven individuals that underwent tumor regression with those of three infected individuals that did not. We found three highly differentiated candidate genomic regions containing several genes related to immune response and/or cancer risk, indicating that the genomic basis of tumor regression was polygenic. Within these genomic regions, we identified putative regulatory variation in candidate genes but no nonsynonymous variation, suggesting that natural tumor regression may be driven, at least in part, by differential host expression of key loci. Comparative oncology can provide insight into the genetic basis of cancer risk, tumor development, and the pathogenicity of cancer, particularly due to our limited ability to monitor natural, untreated tumor progression in human patients. Our results support the hypothesis that host immune response is necessary for triggering tumor regression, providing candidate genes that may translate to novel treatments in human and nonhuman cancers.


Assuntos
Marsupiais/genética , Regressão Neoplásica Espontânea/genética , Animais , Feminino , Variação Estrutural do Genoma , Mutação INDEL , Masculino , Herança Multifatorial , Neoplasias , Polimorfismo de Nucleotídeo Único , Elementos Reguladores de Transcrição
8.
Mol Ecol ; 27(21): 4189-4199, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30171778

RESUMO

Identifying the genetic architecture of complex phenotypes is a central goal of modern biology, particularly for disease-related traits. Genome-wide association methods are a classical approach for identifying the genomic basis of variation in disease phenotypes, but such analyses are particularly challenging in natural populations due to sample size difficulties. Extensive mark-recapture data, strong linkage disequilibrium and a lethal transmissible cancer make the Tasmanian devil (Sarcophilus harrisii) an ideal model for such an association study. We used a RAD-capture approach to genotype 624 devils at ~16,000 loci and then used association analyses to assess the heritability of three cancer-related phenotypes: infection case-control (where cases were infected devils and controls were devils that were never infected), age of first infection and survival following infection. The SNP array explained much of the phenotypic variance for female survival (>80%) and female case-control (>61%). We found that a few large-effect SNPs explained much of the variance for female survival (~5 SNPs explained >61% of the total variance), whereas more SNPs (~56) of smaller effect explained less of the variance for female case-control (~23% of the total variance). By contrast, these same SNPs did not account for a significant proportion of phenotypic variance in males, suggesting that the genetic bases of these traits and/or selection differ across sexes. Loci involved with cell adhesion and cell-cycle regulation underlay trait variation, suggesting that the devil immune system is rapidly evolving to recognize and potentially suppress cancer growth through these pathways. Overall, our study provided necessary data for genomics-based conservation and management in Tasmanian devils.


Assuntos
Resistência à Doença/genética , Marsupiais/genética , Neoplasias/veterinária , Animais , Conservação dos Recursos Naturais , Espécies em Perigo de Extinção , Feminino , Estudos de Associação Genética/veterinária , Genômica , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Taxa de Sobrevida , Tasmânia
9.
Conserv Genet ; 18(4): 977-982, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28966567

RESUMO

Tasmanian devils face a combination of threats to persistence, including Devil Facial Tumor Disease (DFTD), an epidemic transmissible cancer. We used RAD sequencing to investigate genome-wide patterns of genetic diversity and geographic population structure. Consistent with previous results, we found very low genetic diversity in the species as a whole, and we detected two broad genetic clusters occupying the northwestern portion of the range, and the central and eastern portions. However, these two groups overlap across a broad geographic area, and differentiation between them is modest (FST = 0.1081). Our results refine the geographic extent of the zone of mixed ancestry and substructure within it, potentially informing management of genetic variation that existed in pre-diseased populations of the species. DFTD has spread across both genetic clusters, but recent evidence points to a genomic response to selection imposed by DFTD. Any allelic variation for resistance to DFTD may be able to spread across the devil population under selection by DFTD, and/or be present as standing variation in both genetic regions.

10.
Nat Commun ; 7: 12684, 2016 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-27575253

RESUMO

Although cancer rarely acts as an infectious disease, a recently emerged transmissible cancer in Tasmanian devils (Sarcophilus harrisii) is virtually 100% fatal. Devil facial tumour disease (DFTD) has swept across nearly the entire species' range, resulting in localized declines exceeding 90% and an overall species decline of more than 80% in less than 20 years. Despite epidemiological models that predict extinction, populations in long-diseased sites persist. Here we report rare genomic evidence of a rapid, parallel evolutionary response to strong selection imposed by a wildlife disease. We identify two genomic regions that contain genes related to immune function or cancer risk in humans that exhibit concordant signatures of selection across three populations. DFTD spreads between hosts by suppressing and evading the immune system, and our results suggest that hosts are evolving immune-modulated resistance that could aid in species persistence in the face of this devastating disease.


Assuntos
Evolução Biológica , Doenças Transmissíveis Emergentes/veterinária , Resistência à Doença/genética , Neoplasias Faciais/veterinária , Marsupiais/genética , Animais , Doenças Transmissíveis Emergentes/genética , Doenças Transmissíveis Emergentes/transmissão , Resistência à Doença/imunologia , Espécies em Perigo de Extinção , Extinção Biológica , Neoplasias Faciais/genética , Neoplasias Faciais/imunologia , Genômica/métodos , Técnicas de Genotipagem/métodos , Marsupiais/imunologia , Dinâmica Populacional , Tasmânia , Fatores de Tempo
11.
Curr Biol ; 25(16): 2158-65, 2015 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-26234211

RESUMO

The golden jackal of Africa (Canis aureus) has long been considered a conspecific of jackals distributed throughout Eurasia, with the nearest source populations in the Middle East. However, two recent reports found that mitochondrial haplotypes of some African golden jackals aligned more closely to gray wolves (Canis lupus), which is surprising given the absence of gray wolves in Africa and the phenotypic divergence between the two species. Moreover, these results imply the existence of a previously unrecognized phylogenetically distinct species despite a long history of taxonomic work on African canids. To test the distinct-species hypothesis and understand the evolutionary history that would account for this puzzling result, we analyzed extensive genomic data including mitochondrial genome sequences, sequences from 20 autosomal loci (17 introns and 3 exon segments), microsatellite loci, X- and Y-linked zinc-finger protein gene (ZFX and ZFY) sequences, and whole-genome nuclear sequences in African and Eurasian golden jackals and gray wolves. Our results provide consistent and robust evidence that populations of golden jackals from Africa and Eurasia represent distinct monophyletic lineages separated for more than one million years, sufficient to merit formal recognition as different species: C. anthus (African golden wolf) and C. aureus (Eurasian golden jackal). Using morphologic data, we demonstrate a striking morphologic similarity between East African and Eurasian golden jackals, suggesting parallelism, which may have misled taxonomists and likely reflects uniquely intense interspecific competition in the East African carnivore guild. Our study shows how ecology can confound taxonomy if interspecific competition constrains size diversification.


Assuntos
Evolução Biológica , Genoma , Chacais/genética , Lobos/genética , África , Animais , Feminino , Chacais/classificação , Masculino , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Lobos/classificação
12.
J Parasitol ; 99(5): 827-34, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23638969

RESUMO

Species of Syringophilopsis quill mites are found in the flight feathers of passerine birds. A phylogeny of species from this genus infecting North American passerines was inferred from the mitochondrial cytochrome oxidase I gene and the nuclear 28S ribosomal RNA gene. Based on the large genetic distance among lineages, the genus appears to be composed of several cryptic species. A reconciliation analysis of these mites and their avian hosts indicates a limited, but significant, degree of cophylogeny. However, strict cospeciation is not found to be occurring in this system.


Assuntos
Doenças das Aves/parasitologia , Plumas/parasitologia , Infestações por Ácaros/veterinária , Ácaros/classificação , Passeriformes/parasitologia , Animais , Teorema de Bayes , Evolução Biológica , DNA Mitocondrial/química , DNA Ribossômico/química , Complexo IV da Cadeia de Transporte de Elétrons/genética , Especiação Genética , Interações Hospedeiro-Parasita , Infestações por Ácaros/parasitologia , Ácaros/anatomia & histologia , Ácaros/genética , Mitocôndrias/enzimologia , América do Norte , Passeriformes/classificação , Passeriformes/genética , Filogenia , RNA Ribossômico 28S/genética , Alinhamento de Sequência
13.
Syst Parasitol ; 79(3): 201-11, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21643897

RESUMO

Four new syringophilid species of Syringophiloidus Kethley, 1970 are described from North American passerines: S. zonotrichia n. sp. from Zonotrichia albicolis (Gmelin) (Emberizidae) on Texas; S. jackowiaki n. sp. from Poecile carolinensis (Auduborn) (Paridae) in Texas; and S. xanthocephalus n. sp. from Xanthocephalus xanthocephalus (Bonaparte) (Icteridae) and S. agelaius n. sp. from Agelaius phoeniceus Linnaeus (Icteridae), both from Arizona. Spizella breweri (Cassin) (Emberizidae) from California is a new host for Syringophiloidus sialius Skoracki, Flannery & Spicer, 2009; and Melospiza lincolnii (Auduborn) (Emberizidae) from Texas and Vermivora ruficapilla (Wilson) (Parulidae) from California are new hosts for S. seiuri (Ckark, 1964). S. daberti Bochkov, Fain & Skoracki, 2004 from Passerina ciris Linnaeus (Cardinalidae) is recorded in the USA for the first time. A table with the host associations and distribution of all of the North American species of Syringophiloidus is given.


Assuntos
Doenças das Aves/parasitologia , Plumas/parasitologia , Infestações por Ácaros/veterinária , Ácaros/anatomia & histologia , Ácaros/classificação , Passeriformes/parasitologia , Animais , Arizona , California , Feminino , Masculino , Infestações por Ácaros/parasitologia , Texas
14.
J Med Entomol ; 47(5): 727-42, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20939365

RESUMO

Five new species of the genus Picobia are described and illustrated: (1) P. leucophaeus sp. nov. from the Laughing Gull Leucophaeus atricilla L. (Charadriiformes: Laridae) from Texas; (2) P. troglodytes sp. nov. from the House Wren Troglodytes aedon Vieillot (Passeriformes: Troglodytidae) from California; (3) P. cardinalis sp. nov. from the Northern Cardinal Cardinalis cardinalis (L.) (Passeriformes: Cardinalidae) from Texas; (4) P. carpodacus sp. nov. from the Purple Finch Carpodacus purpureus (Gmelin) (Passeriformes: Fringillidae) from California; and (5) P. psaltriparus sp. nov. from the Bushtit Psaltriparus minimus (Townsend) (Passeriformes: Aegithalidae) from Texas. Two avian species from the family Picidae (Piciformes) are recorded as new hosts for P. dryobatis (Fritsch, 1958): the Downy Woodpecker Picoides pubescens (L.) from Texas and the Ladder-backed Woodpecker Picoides scalaris (Wagler) from California. Additionally, all named species of the genus Picobia with their host associations and distributions are summarized in tabular form.


Assuntos
Charadriiformes , Ácaros/anatomia & histologia , Ácaros/classificação , Animais , Doenças das Aves/parasitologia , California , Feminino , Masculino , Infestações por Ácaros/parasitologia , Infestações por Ácaros/veterinária , Passeriformes , Texas
15.
Syst Parasitol ; 76(2): 131-44, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20437219

RESUMO

Four new species belonging to Aulonastus Kethley, 1970 (Acari: Prostigmata: Syringophilidae), which are found inside the quills of body feathers of North American passerines (Aves: Passeriformes), are described and figured: A. emberizicus n. sp. from Ammodramus savanarum (Gmelin) (Emberizidae) (type-host) in Texas, Zonotrichia atricapilla (Gmelin) (Emberizidae) in California and Passerculus sandwichensis (Gmelin) (Emberizidae) in Texas; A. euphagus n. sp. from Euphagus cyanocephalus (Wagler) (Icteridae) in California; A. pirangus n. sp. from Piranga ludoviciana (Wilson) (Cardinalidae) in California; and A. sturnellus n. sp. from Sturnella magna (Linnaeus) (Icteridae) in Texas. A key to females of the known species of Aulonastus is presented.


Assuntos
Doenças dos Peixes/parasitologia , Infestações por Ácaros/veterinária , Ácaros/anatomia & histologia , Ácaros/classificação , Passeriformes/parasitologia , Animais , Plumas/parasitologia , Feminino , Masculino , Infestações por Ácaros/parasitologia , América do Norte , Especificidade da Espécie
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