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1.
Sci Rep ; 14(1): 5162, 2024 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431688

RESUMO

Ophidiomycosis is an emerging infectious disease affecting wild snakes in the Northern Hemisphere. Recently confirmed in Great Britain, the prevalence, severity and significance of ophidiomycosis has yet to be characterised in free-living snakes at a population level in Europe. Therefore, a population of barred grass snakes (Natrix helvetica) in eastern England was monitored for three seasons (May 2019 to October 2021), to investigate the prevalence (25.5%; 191/750 snakes) and severity of skin lesions and their aetiology. The most frequently observed skin lesion characteristics were changes in scale colour, crusting, and scale margin erosion. The majority of such lesions (96.9%; 185/191 snakes) was observed on the ventral surface along the length of the body. The severity of skin lesions was considered mild in more than half of the cases (53.1%; 98/191 snakes). Predominantly, skin lesions were observed in adult snakes (72.8%; 139/191 snakes). Combined histological examinations and qPCR tests of skin lesions from N. helvetica sloughs and/or carcasses confirmed a diagnosis of ophidiomycosis. Further targeted surveillance, supported by molecular and histological examinations to confirm skin lesion aetiology, is required to determine the extent to which our findings reflect the occurrence of ophidiomycosis in populations within wider landscapes.


Assuntos
Colubridae , Dermatopatias , Animais , Humanos , Prevalência , Serpentes , Europa (Continente) , Reino Unido
2.
PeerJ ; 11: e16682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38130921

RESUMO

Gut-associated microbial communities are known to play a vital role in the health and fitness of their hosts. Though studies investigating the factors associated with among-individual variation in microbiome structure in wild animal species are increasing, knowledge of this variation at the individual level is scarce, despite the clear link between microbiome and nutritional status uncovered in humans and model organisms. Here, we combine detailed observational data on life history and foraging preference with 16S rRNA profiling of the faecal microbiome to investigate the relationship between diet, microbiome stability and rates of body mass gain in a migratory capital-breeding bird, the light-bellied Brent goose (Branta bernicla hrota). Our findings suggest that generalist feeders have microbiomes that are intermediate in diversity and composition between two foraging specialisms, and also show higher within-individual plasticity. We also suggest a link between foraging phenotype and the rates of mass gain during the spring staging of a capital breeder. This study offers rare insight into individual-level temporal dynamics of the gut microbiome of a wild host. Further work is needed to uncover the functional link between individual dietary choices, gut microbiome structure and stability, and the implications this has for the reproductive success of this capital breeder.


Assuntos
Microbioma Gastrointestinal , Gansos , Animais , Bactérias , Dieta/veterinária , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Gansos/microbiologia , Tamanho Corporal
3.
Front Microbiol ; 14: 1111018, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36891392

RESUMO

In response to the current worldwide amphibian extinction crisis, conservation instances have encouraged the establishment of ex-situ collections for endangered species. The resulting assurance populations are managed under strict biosecure protocols, often involving artificial cycles of temperature and humidity to induce active and overwintering phases, which likely affect the bacterial symbionts living on the amphibian skin. However, the skin microbiota is an important first line of defense against pathogens that can cause amphibian declines, such as the chytrid Batrachochytrium dendrobatidis (Bd). Determining whether current husbandry practices for assurance populations might deplete amphibians from their symbionts is therefore essential to conservation success. Here, we characterize the effect of the transitions from the wild to captivity, and between aquatic and overwintering phases, on the skin microbiota of two newt species. While our results confirm differential selectivity of skin microbiota between species, they underscore that captivity and phase-shifts similarly affect their community structure. More specifically, the translocation ex-situ is associated with rapid impoverishment, decrease in alpha diversity and strong species turnover of bacterial communities. Shifts between active and overwintering phases also cause changes in the diversity and composition of the microbiota, and on the prevalence of Bd-inhibitory phylotypes. Altogether, our results suggest that current husbandry practices strongly restructure the amphibian skin microbiota. Although it remains to be determined whether these changes are reversible or have deleterious effects on their hosts, we discuss methods to limit microbial diversity loss ex-situ and emphasize the importance of integrating bacterial communities to applied amphibian conservation.

4.
Mol Phylogenet Evol ; 178: 107630, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36182053

RESUMO

We examine the phylogeny of sea pens using sequences of whole mitochondrial genomes and the nuclear ribosomal cluster generated through low coverage Illumina sequencing. Taxon sampling includes 30 species in 19 genera representing 13 families. Ancestral state reconstruction shows that most sea pen mitochondrial genomes have the ancestral gene order, and that Pennatulacea with diverse gene orders are found in a single clade. The monophyly of Pennatulidae and Protoptilidae are rejected by both the mitochondrial and nuclear dataset, while the mitochondrial dataset further rejects monophyly of Virgulariidae, and the nuclear dataset rejects monophyly of Kophobelemnidae. We show discordance between nuclear ribosomal gene cluster phylogenies and whole mitochondrial genome phylogenies and highlight key Pennatulacea taxa that could be included in cnidarian genome-wide studies to better resolve the sea pen tree of life. We further illustrate how well frequently sequenced markers capture the overall diversity of the mitochondrial genome and the nuclear ribosomal genes in sea pens.


Assuntos
Antozoários , Genoma Mitocondrial , Humanos , Animais , Filogenia , Evolução Molecular , Antozoários/genética , Ordem dos Genes
6.
Microbiome ; 10(1): 44, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35272699

RESUMO

BACKGROUND: The fungal pathogen Batrachochytrium dendrobatidis (Bd) threatens amphibian biodiversity and ecosystem stability worldwide. Amphibian skin microbial community structure has been linked to the clinical outcome of Bd infections, yet its overall functional importance is poorly understood. METHODS: Microbiome taxonomic and functional profiles were assessed using high-throughput bacterial 16S rRNA and fungal ITS2 gene sequencing, bacterial shotgun metagenomics and skin mucosal metabolomics. We sampled 56 wild midwife toads (Alytes obstetricans) from montane populations exhibiting Bd epizootic or enzootic disease dynamics. In addition, to assess whether disease-specific microbiome profiles were linked to microbe-mediated protection or Bd-induced perturbation, we performed a laboratory Bd challenge experiment whereby 40 young adult A. obstetricans were exposed to Bd or a control sham infection. We measured temporal changes in the microbiome as well as functional profiles of Bd-exposed and control animals at peak infection. RESULTS: Microbiome community structure and function differed in wild populations based on infection history and in experimental control versus Bd-exposed animals. Bd exposure in the laboratory resulted in dynamic changes in microbiome community structure and functional differences, with infection clearance in all but one infected animal. Sphingobacterium, Stenotrophomonas and an unclassified Commamonadaceae were associated with wild epizootic dynamics and also had reduced abundance in laboratory Bd-exposed animals that cleared infection, indicating a negative association with Bd resistance. This was further supported by microbe-metabolite integration which identified functionally relevant taxa driving disease outcome, of which Sphingobacterium and Bd were most influential in wild epizootic dynamics. The strong correlation between microbial taxonomic community composition and skin metabolome in the laboratory and field is inconsistent with microbial functional redundancy, indicating that differences in microbial taxonomy drive functional variation. Shotgun metagenomic analyses support these findings, with similar disease-associated patterns in beta diversity. Analysis of differentially abundant bacterial genes and pathways indicated that bacterial environmental sensing and Bd resource competition are likely to be important in driving infection outcomes. CONCLUSIONS: Bd infection drives altered microbiome taxonomic and functional profiles across laboratory and field environments. Our application of multi-omics analyses in experimental and field settings robustly predicts Bd disease dynamics and identifies novel candidate biomarkers of infection. Video Abstract.


Assuntos
Quitridiomicetos , Microbiota , Micoses , Animais , Anuros/genética , Anuros/microbiologia , Quitridiomicetos/genética , Microbiota/genética , Micoses/microbiologia , Micoses/veterinária , RNA Ribossômico 16S/genética
7.
Mol Ecol ; 30(22): 5831-5843, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34494339

RESUMO

Social environments influence multiple traits of individuals including immunity, stress and ageing, often in sex-specific ways. The composition of the microbiome (the assemblage of symbiotic microorganisms within a host) is determined by environmental factors and the host's immune, endocrine and neural systems. The social environment could alter host microbiomes extrinsically by affecting transmission between individuals, probably promoting homogeneity in the microbiome of social partners. Alternatively, intrinsic effects arising from interactions between the microbiome and host physiology (the microbiota-gut-brain axis) could translate social stress into dysbiotic microbiomes, with consequences for host health. We investigated how manipulating social environments during larval and adult life-stages altered the microbiome composition of Drosophila melanogaster fruit flies. We used social contexts that particularly alter the development and lifespan of males, predicting that any intrinsic social effects on the microbiome would therefore be sex-specific. The presence of adult males during the larval stage significantly altered the microbiome of pupae of both sexes. In adults, same-sex grouping increased bacterial diversity in both sexes. Importantly, the microbiome community structure of males was more sensitive to social contact at older ages, an effect partially mitigated by housing focal males with young rather than coaged groups. Functional analyses suggest that these microbiome changes impact ageing and immune responses. This is consistent with the hypothesis that the substantial effects of the social environment on individual health are mediated through intrinsic effects on the microbiome, and provides a model for understanding the mechanistic basis of the microbiota-gut-brain axis.


Assuntos
Drosophila melanogaster , Microbiota , Fatores Etários , Animais , Eixo Encéfalo-Intestino , Drosophila melanogaster/genética , Feminino , Masculino , Microbiota/genética , Meio Social
8.
Mayo Clin Proc ; 96(2): 429-437, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33549262

RESUMO

The COVID-19 pandemic accelerated adoption of telemedicine visits into American medicine. It is commonly believed that, within a matter of weeks, telemedicine was widely and successfully implemented and that medicine is forever changed. The experience on the ground, however, is more nuanced, with both positive and negative experiences for patients and clinicians. Advanced models of team-based care with in-room support (aTBC) have developed over the past decade, with strategic delegation of tasks to uptrained support staff, allowing physicians to provide undivided attention to their patients and greater access to care for their populations. Herein, we describe our initial experiences with telemedicine in the context of many years practicing in aTBC models. Our experience demonstrates that when implementing telemedicine visits, it is important to avoid a reflex reversion to the outmoded model of the physician alone in the room with the patient and instead bring forth the safety, quality, and satisfaction advantages associated with aTBC. We provide a practical "how-to" guide for implementing telemedicine visits; outline logistical details of representative video and audio visits from our own practices; describe new opportunities for family engagement, care coordination, and comanagement across specialties; and outline a research agenda going forward to further knowledge of the risks and benefits and optimal application of health care on a telemedicine platform.


Assuntos
COVID-19 , Equipe de Assistência ao Paciente , Telemedicina , Humanos
9.
Mol Ecol ; 30(5): 1322-1335, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33411382

RESUMO

Microbiome-pathogen interactions are increasingly recognized as an important element of host immunity. While these host-level interactions will have consequences for community disease dynamics, the factors which influence host microbiomes at larger scales are poorly understood. We here describe landscape-scale pathogen-microbiome associations within the context of post-epizootic amphibian chytridiomycosis, a disease caused by the panzootic chytrid fungus Batrachochytrium dendrobatidis. We undertook a survey of Neotropical amphibians across altitudinal gradients in Ecuador ~30 years following the observed amphibian declines and collected skin swab-samples which were metabarcoded using both fungal (ITS-2) and bacterial (r16S) amplicons. The data revealed marked variation in patterns of both B. dendrobatidis infection and microbiome structure that are associated with host life history. Stream breeding amphibians were most likely to be infected with B. dendrobatidis. This increased probability of infection was further associated with increased abundance and diversity of non-Batrachochytrium chytrid fungi in the skin and environmental microbiome. We also show that increased alpha diversity and the relative abundance of fungi are lower in the skin microbiome of adult stream amphibians compared to adult pond-breeding amphibians, an association not seen for bacteria. Finally, stream tadpoles exhibit lower proportions of predicted protective microbial taxa than pond tadpoles, suggesting reduced biotic resistance. Our analyses show that host breeding ecology strongly shapes pathogen-microbiome associations at a landscape scale, a trait that may influence resilience in the face of emerging infectious diseases.


Assuntos
Quitridiomicetos , Microbiota , Micoses , Anfíbios , Animais , Quitridiomicetos/genética , Equador , Microbiota/genética , Micoses/veterinária
10.
Carcinogenesis ; 42(2): 220-231, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32780107

RESUMO

Prostate cancer is the second most common type of cancer and the second leading cause of cancer death in American men. RAD9 stabilizes the genome, but prostate cancer cells and tumors often have high quantities of the protein. Reduction of RAD9 level within prostate cancer cells decreases tumorigenicity of nude mouse xenographs and metastasis phenotypes in culture, indicating that RAD9 overproduction is essential for the disease. In prostate cancer DU145 cells, CpG hypermethylation in a transcription suppressor site of RAD9 intron 2 causes high-level gene expression. Herein, we demonstrate that DNA methyltransferases DNMT1 and DNMT3B are highly abundant in prostate cancer cells DU145, CWR22, LNCaP and PC-3; yet, these DNMTs bind primarily to the transcription suppressor in DU145, the only cells where methylation is critical for RAD9 regulation. For DU145 cells, DNMT1 or DNMT3B shRNA reduced RAD9 level and tumorigenicity, and RAD9 ectopic expression restored this latter activity in the DNMT knockdown cells. High levels of RAD9, DNMT1, DNMT3B and RAD9 transcription suppressor hypermethylation were significantly correlated in prostate tumors, and not in normal prostate tissues. Based on these results, we propose a novel model where RAD9 is regulated epigenetically by DNMT1 and DNMT3B, via targeted hypermethylation, and that consequent RAD9 overproduction promotes prostate tumorigenesis.


Assuntos
Carcinogênese/genética , Proteínas de Ciclo Celular/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Neoplasias da Próstata/genética , Animais , Linhagem Celular Tumoral , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Próstata/patologia , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Front Microbiol ; 10: 1834, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507541

RESUMO

The emerging fungal pathogen, Batrachochytrium salamandrivorans (Bsal) is responsible for the catastrophic decline of European salamanders and poses a threat to amphibians globally. The amphibian skin microbiome can influence disease outcome for several host-pathogen systems, yet little is known of its role in Bsal infection. In addition, many experimental in-vivo amphibian disease studies to date have relied on specimens that have been kept in captivity for long periods without considering the influence of environment on the microbiome and how this may impact the host response to pathogen exposure. We characterized the impact of captivity and exposure to Bsal on the skin bacterial and fungal communities of two co-occurring European newt species, the smooth newt, Lissotriton vulgaris and the great-crested newt, Triturus cristatus. We show that captivity led to significant losses in bacterial and fungal diversity of amphibian skin, which may be indicative of a decline in microbe-mediated protection. We further demonstrate that in both L. vulgaris and T. cristatus, Bsal infection was associated with changes in the composition of skin bacterial communities with possible negative consequences to host health. Our findings advance current understanding of the role of host-associated microbiota in Bsal infection and highlight important considerations for ex-situ amphibian conservation programmes.

12.
Mitochondrial DNA A DNA Mapp Seq Anal ; 30(6): 764-777, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31317811

RESUMO

We present the first documented complete mitogenomes of deep-sea Pennatulacea, representing nine genera and eight families. These include one species each of the deep-sea genera Funiculina, Halipteris, Protoptilum and Distichoptilum, four species each of Umbellula and Pennatula, three species of Kophobelemnon and two species of Anthoptilum, as well as one species of the epi- and mesobenthic genus Virgularia. Seventeen circular genomes ranged from 18,513 bp (Halipteris cf. finmarchica) to 19,171 bp (Distichoptilum gracile) and contained all genes standard to octocoral mitochondrial genomes (14 protein-coding genes, two ribosomal RNA genes and one transfer RNA). We found at least three different gene orders in Pennatulacea: the ancestral gene order, the gene order found in bamboo corals (Family Isididae), and a novel gene order. The mitogenome of one species of Umbellula has a bipartite genome (∼13 kbp and ∼5 kbp), with good evidence that both parts are circular.


Assuntos
Antozoários/genética , Código de Barras de DNA Taxonômico , Genoma Mitocondrial/genética , RNA Ribossômico/genética , RNA de Transferência/genética , Animais , Irlanda , Especificidade da Espécie
13.
Front Microbiol ; 10: 1245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281291

RESUMO

There is growing appreciation of the important role of commensal microbes in ensuring the normal function and health of their hosts, including determining how hosts respond to pathogens. A range of infectious diseases are threatening amphibians worldwide, and evidence is accumulating that the host-associated bacteria that comprise the microbiome may be key in mediating interactions between amphibian hosts and infectious pathogens. We used 16S rRNA amplicon sequencing to quantify the skin microbial community structure of over 200 individual wild adult European common frogs (Rana temporaria), from ten populations with contrasting history of the lethal disease ranavirosis, caused by emerging viral pathogens belonging to the genus Ranavirus. All populations had similar species richness irrespective of disease history, but populations that have experienced historical outbreaks of ranavirosis have a distinct skin microbiome structure (beta diversity) when compared to sites where no outbreaks of the disease have occurred. At the individual level, neither age, body length, nor sex of the frog could predict the structure of the skin microbiota. Our data potentially support the hypothesis that variation among individuals in skin microbiome structure drive differences in susceptibility to infection and lethal outbreaks of disease. More generally, our results suggest that population-level processes are more important for driving differences in microbiome structure than variation among individuals within populations in key life history traits such as age and body size.

14.
Carcinogenesis ; 40(1): 164-172, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30295739

RESUMO

RAD9A plays an important role in prostate tumorigenesis and metastasis-related phenotypes. The protein classically functions as part of the RAD9A-HUS1-RAD1 complex but can also act independently. RAD9A can selectively transactivate multiple genes, including CDKN1A and NEIL1 by binding p53-consensus sequences in or near promoters. RAD9A is overexpressed in human prostate cancer specimens and cell lines; its expression correlates with tumor progression. Silencing RAD9A in prostate cancer cells impairs their ability to form tumors in vivo and migrate as well as grow anchorage independently in vitro. We demonstrate herein that RAD9A transcriptionally controls AGR2, a gene aberrantly overexpressed in patients with metastatic prostate cancer. Transient or stable knockdown of RAD9A in PC-3 cells caused downregulation of AGR2 protein abundance. Reduced AGR2 protein levels were due to lower abundance of AGR2 mRNA. The AGR2 genomic region upstream of the coding initiation site contains several p53 consensus sequences. RAD9A bound specifically to the 5'-untranslated region of AGR2 in PC-3 cells at a partial p53 consensus sequence at position +3136 downstream from the transcription start site, determined by chromatin immunoprecipitation, followed by PCR amplification. Binding of RAD9A to the p53 consensus sequence was sufficient to drive AGR2 gene transcription, shown by a luciferase reporter assay. In contrast, when the RAD9A-binding sequence on the AGR2 was mutated, no luciferase activity was detected. Knockdown of RAD9A in PC-3 cells impaired cell migration and anchorage-independent growth. However, ectopically expressed AGR2 in RAD9A-depleted PC-3 cells restored these phenotypes. Our results suggest RAD9A drives metastasis by controlling AGR2 abundance.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Neoplasias da Próstata/patologia , Proteínas/genética , Linhagem Celular Tumoral , Movimento Celular , Humanos , Masculino , Mucoproteínas , Metástase Neoplásica , Proteínas Oncogênicas , Fenótipo , RNA Mensageiro/análise , Transcrição Gênica
15.
Front Microbiol ; 10: 2883, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31956320

RESUMO

Variation among animals in their host-associated microbial communities is increasingly recognized as a key determinant of important life history traits including growth, metabolism, and resistance to disease. Quantitative estimates of the factors shaping the stability of host microbiomes over time at the individual level in non-model organisms are scarce. Addressing this gap in our knowledge is important, as variation among individuals in microbiome stability may represent temporal gain or loss of key microbial species and functions linked to host health and/or fitness. Here we use controlled experiments to investigate how both heterogeneity in microbial species richness of the environment and exposure to the emerging pathogen Ranavirus influence the structure and temporal dynamics of the skin microbiome in a vertebrate host, the European common frog (Rana temporaria). Our evidence suggests that altering the bacterial species richness of the environment drives divergent temporal microbiome dynamics of the amphibian skin. Exposure to ranavirus effects changes in skin microbiome structure irrespective of total microbial diversity, but individuals with higher pre-exposure skin microbiome diversity appeared to exhibit higher survival. Higher diversity skin microbiomes also appear less stable over time compared to lower diversity microbiomes, but stability of the 100 most abundant ("core") community members was similar irrespective of microbiome richness. Our study highlights the importance of extrinsic factors in determining the stability of host microbiomes over time, which may in turn have important consequences for the stability of host-microbe interactions and microbiome-fitness correlations.

16.
PLoS One ; 13(11): e0206220, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30485275

RESUMO

The deep sea is the largest biome on earth, and microbes dominate in biomass and abundance. Anthropogenic litter is now almost ubiquitous in this biome, and its deposition creates new habitats and environments, including for microbial assemblages. With the ever increasing accumulation of this debris, it is timely to identify and describe the bacterial and archaeal communities that are able to form biofilms on macrodebris in the deep sea. Using 16S rRNA gene high throughput sequencing, we show for the first time the composition of bacteria and archaea on macrodebris collected from the deep sea. Our data suggest differences in the microbial assemblage composition across litter of different materials including metal, rubber, glass, fabric and plastic. These results imply that anthropogenic macrodebris provide diverse habitats for bacterial and archaeal biofilms and each may harbour distinct microbial communities.


Assuntos
Archaea/metabolismo , Bactérias/metabolismo , Biodiversidade , Atividades Humanas , Resíduos , Oceano Atlântico , Biofilmes , Geografia , Sedimentos Geológicos/microbiologia , Humanos , Filogenia , Água do Mar
17.
Sci Rep ; 8(1): 13942, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30224824

RESUMO

Sporadic cases of herpesvirus-associated disease have been reported in the Western European hedgehog (Erinaceus europaeus), but there has been little surveillance for, nor any sequence characterisation of, herpesviruses in this species to date. A nested pan-herpesvirus polymerase chain reaction (PCR) targeting a region of the DNA polymerase gene was used to test 129 Western European hedgehogs from across Great Britain, 2011-2016; 59 (46%) of which were PCR-positive. In addition, samples from two previously published cases of fatal herpesvirus infection in E. europaeus, from Sweden and Switzerland, were positive using this PCR. No statistically significant relationship was detected between PCR result and sex, age class, year or season for the British hedgehogs tested. In most PCR-positive animals (19/22) from which liver and brain were tested separately, both were PCR-positive. Sanger sequencing of amplicons from 59 British hedgehogs revealed at least two novel viruses within the Gammaherpesvirinae. Thirteen of these hedgehogs had liver and brain tissues screened for microscopic abnormalities, of which one had non-suppurative meningoencephalitis, but neither intranuclear inclusion bodies nor herpesvirus virions (on electron microscopical examination) were identified. Sequencing of the whole DNA polymerase gene confirmed two genetically different Human alphaherpesvirus 1 viruses in the Swedish and Swiss hedgehogs.


Assuntos
Ouriços/virologia , Infecções por Herpesviridae/virologia , Herpesviridae/genética , Animais , Encéfalo/virologia , DNA Polimerase Dirigida por DNA/genética , Feminino , Humanos , Corpos de Inclusão/genética , Masculino , Reação em Cadeia da Polimerase/métodos , Suécia , Suíça , Reino Unido , Vírion/genética
18.
Transl Cancer Res ; 7(Suppl 6): S651-S661, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30079300

RESUMO

Prostate cancer is a complex disease, with multiple subtypes and clinical presentations. Much progress has been made in recent years to understand the underlying genetic basis that drives prostate cancer. Such mechanistic information is useful for development of novel therapeutic targets, to identify biomarkers for early detection or to distinguish between aggressive and indolent disease, and to predict treatment outcome. Multiple tests have become available in recent years to address these clinical needs for prostate cancer. We describe several of these assays, summarizing test details, performance characteristics, and acknowledging their limitations. There is a pressing unmet need for novel biomarkers that can demonstrate improvement in these areas. We introduce one such candidate biomarker, RAD9, describe its functions in the DNA damage response, and detail why it can potentially fill this void. RAD9 has multiple roles in prostate carcinogenesis, making it potentially useful as a clinical tool for men with prostate cancer. RAD9 was originally identified as a radioresistance gene, and subsequent investigations revealed several key functions in the response of cells to DNA damage, including involvement in cell cycle checkpoint control, at least five DNA repair pathways, and apoptosis. Further studies indicated aberrant overexpression in approximately 45% of prostate tumors, with a strong correlation between RAD9 abundance and cancer stage. A causal relationship between RAD9 and prostate cancer was first demonstrated using a mouse model, where tumorigenicity of human prostate cancer cells after subcutaneous injection into nude mice was diminished when RNA interference was used to reduce the normally high levels of the protein. In addition to activity needed for the initial development of tumors, cell culture studies indicated roles for RAD9 in promoting prostate cancer progression by controlling cell migration and invasion through regulation of ITGB1 protein levels, and anoikis resistance by modulating AKT activation. Furthermore, RAD9 enhances the resistance of human prostate cancer cells to radiation in part by regulating ITGB1 protein abundance. RAD9 binds androgen receptor and inhibits androgen-induced androgen receptor's activity as a transcription factor. Moreover, RAD9 also acts as a gene-specific transcription factor, through binding p53 consensus sequences at target gene promoters, and this likely contributes to its oncogenic activity. Given these diverse and extensive activities, RAD9 plays important roles in the initiation and progression of prostate cancer and can potentially serve as a valuable biomarker useful in the management of patients with this disease.

19.
ISME J ; 12(10): 2506-2517, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29942072

RESUMO

Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases.


Assuntos
Anfíbios/genética , Quitridiomicetos , Microbiota , Micoses/veterinária , Anfíbios/microbiologia , Animais , Anuros , Predisposição Genética para Doença , Micoses/epidemiologia , Micoses/microbiologia , Pele/microbiologia , África do Sul/epidemiologia
20.
Nat Commun ; 9(1): 693, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29449565

RESUMO

Host-associated microbes are vital for combatting infections and maintaining health. In amphibians, certain skin-associated bacteria inhibit the fungal pathogen Batrachochytrium dendrobatidis (Bd), yet our understanding of host microbial ecology and its role in disease outbreaks is limited. We sampled skin-associated bacteria and Bd from Pyrenean midwife toad populations exhibiting enzootic or epizootic disease dynamics. We demonstrate that bacterial communities differ between life stages with few shared taxa, indicative of restructuring at metamorphosis. We detected a significant effect of infection history on metamorph skin microbiota, with reduced bacterial diversity in epizootic populations and differences in community structure and predicted function. Genome sequencing of Bd isolates supports a single introduction to the Pyrenees and reveals no association between pathogen genetics and epidemiological trends. Our findings provide an ecologically relevant insight into the microbial ecology of amphibian skin and highlight the relative importance of host microbiota and pathogen genetics in predicting disease outcome.


Assuntos
Antibiose/fisiologia , Anuros/microbiologia , Bactérias/classificação , Quitridiomicetos/patogenicidade , Micoses/prevenção & controle , Micoses/veterinária , Pele/microbiologia , Animais , Bactérias/isolamento & purificação , Fenômenos Fisiológicos Bacterianos , Quitridiomicetos/genética , Microbiota/genética , Micoses/microbiologia
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