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1.
Phytopathology ; 114(5): 837-842, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38815216

RESUMO

Plant diseases significantly impact food security and food safety. It was estimated that food production needs to increase by 50% to feed the projected 9.3 billion people by 2050. Yet, plant pathogens and pests are documented to cause up to 40% yield losses in major crops, including maize, rice, and wheat, resulting in annual worldwide economic losses of approximately US$220 billion. Yield losses due to plant diseases and pests are estimated to be 21.5% (10.1 to 28.1%) in wheat, 30.3% (24.6 to 40.9%) in rice, and 22.6% (19.5 to 41.4%) in maize. In March 2023, The American Phytopathological Society (APS) conducted a survey to identify and rank key challenges in plant pathology in the next decade. Phytopathology subsequently invited papers that address those key challenges in plant pathology, and these were published as a special issue. The key challenges identified include climate change effect on the disease triangle and outbreaks, plant disease resistance mechanisms and its applications, and specific diseases including those caused by Candidatus Liberibacter spp. and Xylella fastidiosa. Additionally, disease detection, natural and man-made disasters, and plant disease control strategies were explored in issue articles. Finally, aspects of open access and how to publish articles to maximize the Findability, Accessibility, Interoperability, and Reuse of digital assets in plant pathology were described. Only by identifying the challenges and tracking progress in developing solutions for them will we be able to resolve the issues in plant pathology and ultimately ensure plant health, food security, and food safety.


Assuntos
Produtos Agrícolas , Doenças das Plantas , Patologia Vegetal , Doenças das Plantas/microbiologia , Produtos Agrícolas/microbiologia , Resistência à Doença , Mudança Climática , Xylella
2.
Appl Environ Microbiol ; 90(5): e0205623, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38651929

RESUMO

Aspergillus fumigatus is a ubiquitous saprotroph and human-pathogenic fungus that is life-threatening to the immunocompromised. Triazole-resistant A. fumigatus was found in patients without prior treatment with azoles, leading researchers to conclude that resistance had developed in agricultural environments where azoles are used against plant pathogens. Previous studies have documented azole-resistant A. fumigatus across agricultural environments, but few have looked at retail plant products. Our objectives were to determine if azole-resistant A. fumigatus is prevalent in retail plant products produced in the United States (U.S.), as well as to identify the resistance mechanism(s) and population genetic structure of these isolates. Five hundred twenty-five isolates were collected from retail plant products and screened for azole resistance. Twenty-four isolates collected from compost, soil, flower bulbs, and raw peanuts were pan-azole resistant. These isolates had the TR34/L98H, TR46/Y121F/T289A, G448S, and H147Y cyp51A alleles, all known to underly pan-azole resistance, as well as WT alleles, suggesting that non-cyp51A mechanisms contribute to pan-azole resistance in these isolates. Minimum spanning networks showed two lineages containing isolates with TR alleles or the F46Y/M172V/E427K allele, and discriminant analysis of principle components identified three primary clusters. This is consistent with previous studies detecting three clades of A. fumigatus and identifying pan-azole-resistant isolates with TR alleles in a single clade. We found pan-azole resistance in U.S. retail plant products, particularly compost and flower bulbs, which indicates a risk of exposure to these products for susceptible populations and that highly resistant isolates are likely distributed worldwide on these products.IMPORTANCEAspergillus fumigatus has recently been designated as a critical fungal pathogen by the World Health Organization. It is most deadly to people with compromised immune systems, and with the emergence of antifungal resistance to multiple azole drugs, this disease carries a nearly 100% fatality rate without treatment or if isolates are resistant to the drugs used to treat the disease. It is important to determine the relatedness and origins of resistant A. fumigatus isolates in the environment, including plant-based retail products, so that factors promoting the development and propagation of resistant isolates can be identified.


Assuntos
Aspergillus fumigatus , Azóis , Farmacorresistência Fúngica , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Farmacorresistência Fúngica/genética , Azóis/farmacologia , Humanos , Antifúngicos/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Estados Unidos , Microbiologia do Solo , Testes de Sensibilidade Microbiana , Fungicidas Industriais/farmacologia , Arachis/microbiologia
3.
PLoS One ; 18(3): e0282499, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36867648

RESUMO

Aspergillus fumigatus is a ubiquitous fungus, a saprophyte of plants, and an opportunistic pathogen of humans. Azole fungicides are used in agriculture to control plant pathogens, and azoles are also used as a first line of treatment for aspergillosis. The continued exposure of A. fumigatus to azoles in the environment has likely led to azole resistance in the clinic where infections result in high levels of mortality. Pan-azole resistance in environmental isolates is most often associated with tandem-repeat (TR) mutations containing 34 or 46 nucleotides in the cyp51A gene. Because the rapid detection of resistance is important for public health, PCR-based techniques have been developed to detect TR mutations in clinical samples. We are interested in identifying agricultural environments conducive to resistance development, but environmental surveillance of resistance has focused on labor-intensive isolation of the fungus followed by screening for resistance. Our goal was to develop assays for the rapid detection of pan-azole-resistant A. fumigatus directly from air, plants, compost, and soil samples. To accomplish this, we optimized DNA extractions for air filters, soil, compost, and plant debris and standardized two nested-PCR assays targeting the TR mutations. Sensitivity and specificity of the assays were tested using A. fumigatus DNA from wild type and TR-based resistant isolates and with soil and air filters spiked with conidia of the same isolates. The nested-PCR assays were sensitive to 5 fg and specific to A. fumigatus without cross-reaction with DNA from other soil microorganisms. Environmental samples from agricultural settings in Georgia, USA were sampled and tested. The TR46 allele was recovered from 30% of samples, including air, soil and plant debris samples from compost, hibiscus and hemp. These assays allow rapid surveillance of resistant isolates directly from environmental samples improving our identification of hotspots of azole-resistant A. fumigatus.


Assuntos
Compostagem , Solo , Humanos , Aspergillus fumigatus , Azóis , Farmacorresistência Fúngica , Proteínas Fúngicas
4.
Phys Chem Chem Phys ; 25(1): 183-191, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36484232

RESUMO

Momentum vector correlation is a powerful tool to study molecular dissociation. We have studied the three-body fragmentation of carbon disulfide after sulfur 1s photoionization by means of momentum imaging techniques. Concerted and sequential pathways are disentangled in three-body fragmentation using adapted analysis strategies. In particular, we introduce various data visualization schemes that are proved to be particularly efficient to determine dissociation dynamics.


Assuntos
Dissulfeto de Carbono , Enxofre
5.
Clin J Pain ; 38(4): 257-263, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35093956

RESUMO

OBJECTIVE: The present study investigated whether illness cognitions mediated the relationship between caregiving demands and positive and negative indicators of adjustment in partners of patients with chronic pain. METHODS: The sample of this cross-sectional study consisted of 151 partners (mean age=61.4 y, SD=13.6 y, 57% male) of patients with chronic pain (eg, back pain). The study was conducted in the Pain Centre of the University Medical Centre Groningen, The Netherlands, during November 2014 to June 2015. Participants completed questionnaires that assessed caregiving demands, illness cognitions, perceived burden, distress, positive affect, and life satisfaction. RESULTS: The results showed that among illness cognitions, acceptance of the illness mediated the association between caregiving demands and burden (b=0.16, 95% confidence interval [CI]: 0.05-0.28) and positive affect (b=-0.21, CI: -0.41 to -0.06). Helplessness mediated the association between caregiving demands and burden (b=0.46, CI: 0.26-0.69) and distress (b=0.35, CI: 0.19-0.53). Perceived benefits did not mediate any of these associations. The findings indicate that partners who experience more demands tend to appraise the consequences of the patients' pain condition more negatively, which in turn is associated with their emotional adjustment. DISCUSSION: The results suggest that illness cognitions play an important role in the psychological adjustment of partners. Enhancing acceptance of the illness and reducing feelings of helplessness could form the basis of interventions aiming at promoting psychological adjustment in partners, especially when it is difficult to reduce the demands.


Assuntos
Cuidadores , Dor Crônica , Adaptação Psicológica , Cuidadores/psicologia , Cognição , Efeitos Psicossociais da Doença , Estudos Transversais , Ajustamento Emocional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/psicologia , Inquéritos e Questionários
6.
G3 (Bethesda) ; 12(2)2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-34897421

RESUMO

Pathogen resistance to clinical antimicrobial agents is an urgent problem. The fungus Aspergillus fumigatus causes 300,000 life-threatening infections in susceptible humans annually. Azoles, which are widely used in both clinical and agricultural settings, are currently the most effective treatment, but resistance to clinical azoles is emerging worldwide. Here, we report the isolation and analysis of azole-sensitive and azole-resistant A. fumigatus from agricultural environments in the southeastern United States (USA) and show that the USA pan-azole-resistant isolates form a clade with pan-azole-resistant isolates from the United Kingdom, the Netherlands, and India. We show that several pan-azole-resistant isolates from agricultural settings in the USA and India also carry alleles with mutations conferring resistance to agricultural fungicides from the benzimidazole (MBC) and quinone outside inhibitor (QoI) classes. We further show that pan-azole-resistant A. fumigatus isolates from patients in clinical settings in the USA, India, and the Netherlands also carry alleles conferring resistance to MBC and QoI agricultural fungicides. The presence of markers for resistance to agricultural-use fungicides in clinical A. fumigatus isolates is strong evidence for an agricultural origin of pan-azole resistance in patients. The presence of multiple fungicide-resistance alleles in agricultural and clinical isolates further suggests that the unique genetics of the pan-azole-resistant clade enables the evolution and/or persistence of antimicrobial resistance mutations leading to the establishment of multifungicide-resistant isolates.


Assuntos
Anti-Infecciosos , Aspergillus fumigatus , Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Aspergillus fumigatus/genética , Azóis/farmacologia , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Humanos , Testes de Sensibilidade Microbiana
7.
Front Fungal Biol ; 3: 910232, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37746203

RESUMO

Numerous plant-pathogenic fungi secrete necrotrophic effectors (syn. host-selective toxins) that are important determinants of pathogenicity and virulence in species that have a necrotrophic lifestyle. Corynespora cassiicola is a necrotrophic fungus causing emerging target spot epidemics in the southeastern United States (US). Previous studies revealed that populations of C. cassiicola from cotton, soybean, and tomato are clonal, host specialized and genetically distinct. Additionally, cassiicolin - the necrotrophic effector identified in some C. cassiicola isolates - is an important toxin for virulence on rubber. It is encoded by seven Cas gene variants. Our goal was to conduct comparative genomic analyses to identify variation among putative necrotrophic effector genes and to determine if lack of one of the mating-types explained clonal populations in C. cassiicola causing outbreaks in the southeastern US and the apparent absence of sexual reproduction worldwide. A total of 12 C. cassiicola genomes, with four each from isolates from tomato, soybean, and cotton, were sequenced using an Illumina Next Seq platform. Each genome was assembled de novo, compared with the reference genome from rubber, and searched for known Cas, and other gene clusters with homologs of secondary metabolites. Cas2 and/or Cas6 were present in isolates from soybean in the southeastern US, whereas Cas1 and Cas2 were present in isolates from cotton in the southeastern US. In addition, several toxin genes, including the T-toxin biosynthetic genes were present in all C. cassiicola from cotton, soybean, and tomato. The mating-type locus was identified in all of the sequenced genomes, with the MAT1-1 idiomorph present in all cotton isolates and the rubber isolate, whereas the MAT1-2 idiomorph was present in all soybean isolates. We developed a PCR-based marker for mating-type in C. cassiicola. Both mating types were present in isolates from tomato. Thus, C. cassiicola has both mating-types necessary for sexual reproduction, but the absence of both mating-types within soybean and cotton populations could explain clonality in these populations. Variation in necrotrophic effectors may underlie host specialization and disease emergence of target spot on cotton, soybean, and tomato in the southeastern US.

8.
PLoS Genet ; 17(11): e1009868, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34752469

RESUMO

While comprehensive molecular profiling of histone H3.3 mutant pediatric high-grade glioma has revealed extensive dysregulation of the chromatin landscape, the exact mechanisms driving tumor formation remain poorly understood. Since H3.3 mutant gliomas also exhibit high levels of copy number alterations, we set out to address if the H3.3K27M oncohistone leads to destabilization of the genome. Hereto, we established a cell culture model allowing inducible H3.3K27M expression and observed an increase in mitotic abnormalities. We also found enhanced interaction of DNA replication factors with H3.3K27M during mitosis, indicating replication defects. Further functional analyses revealed increased genomic instability upon replication stress, as represented by mitotic bulky and ultrafine DNA bridges. This co-occurred with suboptimal 53BP1 nuclear body formation after mitosis in vitro, and in human glioma. Finally, we observed a decrease in ultrafine DNA bridges following deletion of the K27M mutant H3F3A allele in primary high-grade glioma cells. Together, our data uncover a role for H3.3 in DNA replication under stress conditions that is altered by the K27M mutation, promoting genomic instability and potentially glioma development.


Assuntos
Neoplasias Encefálicas/genética , Replicação do DNA/genética , Instabilidade Genômica , Glioma/genética , Histonas/fisiologia , Neoplasias Encefálicas/patologia , Criança , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Humanos , Mitose/genética
9.
PLoS Pathog ; 17(7): e1009711, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34324607

RESUMO

Aspergillus fumigatus is an opportunistic human pathogen that causes aspergillosis, a spectrum of environmentally acquired respiratory illnesses. It has a cosmopolitan distribution and exists in the environment as a saprotroph on decaying plant matter. Azoles, which target Cyp51A in the ergosterol synthesis pathway, are the primary class of drugs used to treat aspergillosis. Azoles are also used to combat plant pathogenic fungi. Recently, an increasing number of azole-naive patients have presented with pan-azole-resistant strains of A. fumigatus. The TR34/L98H and TR46/Y121F/T289A alleles in the cyp51A gene are the most common ones conferring pan-azole resistance. There is evidence that these mutations arose in agricultural settings; therefore, numerous studies have been conducted to identify azole resistance in environmental A. fumigatus and to determine where resistance is developing in the environment. Here, we summarize the global occurrence of azole-resistant A. fumigatus in the environment based on available literature. Additionally, we have created an interactive world map showing where resistant isolates have been detected and include information on the specific alleles identified, environmental settings, and azole fungicide use. Azole-resistant A. fumigatus has been found on every continent, except for Antarctica, with the highest number of reports from Europe. Developed environments, specifically hospitals and gardens, were the most common settings where azole-resistant A. fumigatus was detected, followed by soils sampled from agricultural settings. The TR34/L98H resistance allele was the most common in all regions except South America where the TR46/Y121F/T289A allele was the most common. A major consideration in interpreting this survey of the literature is sampling bias; regions and environments that have been extensively sampled are more likely to show greater azole resistance even though resistance could be more prevalent in areas that are under-sampled or not sampled at all. Increased surveillance to pinpoint reservoirs, as well as antifungal stewardship, is needed to preserve this class of antifungals for crop protection and human health.


Assuntos
Aspergilose/microbiologia , Aspergillus fumigatus/genética , Farmacorresistência Fúngica/genética , Animais , Antifúngicos , Azóis , Reservatórios de Doenças , Humanos
10.
Mycologia ; 113(3): 586-598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33783338

RESUMO

Neofusicoccum species are endophytes and pathogens of woody hosts and members of the Botryosphaeriaceae. Leaf dieback is a new disease resulting in death of compound leaves and extensive defoliation of pecan trees (Carya illinoinensis) throughout the southeastern United States. Currently, the disease is consistently most severe on trees that are not managed with fungicides for pecan scab. Preliminary observations of the fungus isolated from symptomatic leaves indicated that it was a member of the genus Neofusicoccum. Our objectives were to confirm that this is the causal organism of leaf dieback disease of pecan and to determine whether this disease is caused by a new or previously described species of Neofusicoccum. Morphological observations of pure cultures, conidiomata, conidiogenous cells, and conidia were consistent with members of the genus Neofusicoccum. Using Koch's postulates, we established that Neofusicoccum sp. isolated from symptomatic leaves caused the disease. We sequenced the internal transcribed spacer of the rDNA (ITS), elongation factor 1-α (EF1-α), the second largest subunit of RNA polymerase II (RPB2), and ß-tubulin (TUB2) of 11 isolates collected from Georgia and Texas. Phylogenetic and network analyses of these sequences combined with publicly available sequences of 40 members of the N. parvum-N. ribis species complex and the outgroup N. australe revealed that this fungus is a member of the species complex but is genetically distinct from previously described species. We determined that leaf dieback of pecan is caused by a novel species, named herein N. caryigenum.


Assuntos
Carya , DNA Fúngico/genética , Georgia , Filogenia , Folhas de Planta
11.
Biochim Biophys Acta Mol Basis Dis ; 1867(5): 166089, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33549745

RESUMO

Gaucher disease (GD) is caused by homozygous mutations in the GBA1 gene, which encodes the lysosomal ß-glucosidase (GBA) enzyme. GD affects several organs and tissues, including the brain in certain variants of the disease. Heterozygous GBA1 variants are a major genetic risk factor for developing Parkinson's disease. The RIPK3 kinase is relevant in GD and its deficiency improves the neurological and visceral symptoms in a murine GD model. RIPK3 mediates necroptotic-like cell death: it is unknown whether the role of RIPK3 in GD is the direct induction of necroptosis or if it has a more indirect function by mediating necrosis-independent. Also, the mechanisms that activate RIPK3 in GD are currently unknown. In this study, we show that c-Abl tyrosine kinase participates upstream of RIPK3 in GD. We found that the active, phosphorylated form of c-Abl is increased in several GD models, including patient's fibroblasts and GBA null mice. Furthermore, its pharmacological inhibition with the FDA-approved drug Imatinib decreased RIPK3 signaling. We found that c-Abl interacts with RIPK3, that RIPK3 is phosphorylated at a tyrosine site, and that this phosphorylation is reduced when c-Abl is inhibited. Genetic ablation of c-Abl in neuronal GD and GD mice models significantly reduced RIPK3 activation and MLKL downstream signaling. These results showed that c-Abl signaling is a new upstream pathway that activates RIPK3 and that its inhibition is an attractive therapeutic approach for the treatment of GD.


Assuntos
Apoptose , Doença de Gaucher/patologia , Glucosilceramidase/metabolismo , Neurônios/patologia , Proteínas Proto-Oncogênicas c-abl/fisiologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Animais , Doença de Gaucher/genética , Doença de Gaucher/metabolismo , Glucosilceramidase/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Necroptose , Neurônios/metabolismo , Fosforilação , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Transdução de Sinais
12.
Br J Health Psychol ; 26(2): 401-418, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33180996

RESUMO

OBJECTIVES: Partner's responses to pain behaviours play a pivotal role in the patient's adjustment. This study aims to further our knowledge regarding patients' and partners' interpretation of partners' responses to pain behaviours, and the possible discrepancies between patients' and partners' perceptions. Further, this study examines patients' preferred responses to pain behaviours and possible discrepancies between received and preferred responses to pain behaviours. DESIGN: A qualitative research design based on a semi-structured in-depth interview. METHODS: Patients with chronic low back pain and their partners (n = 54) were recruited through purposive sampling and interviewed. Data were analysed based on an inductive analytic approach. RESULTS: Patients as well as partners indicated a number of different interpretations of partners' responses to pain behaviours, including invalidation, relieving pain, validation, encouragement, caregiving exhaustion, and expressing resentment. Patients and partners revealed similarities in the interpretation of response categories that they associated with validation, invalidation, and expressing resentment. Discrepancies between patients and partners indicated that partners interpreted some responses as caused by caregiving exhaustion while patients did not. Patients perceived partner responses that included the active involvement of the partner (e.g., encouraging pain talk) more positively than responses that showed less active involvement of the partner. CONCLUSION: Patients and partners are likely to make various interpretations of a certain partner response to pain behaviours. Our findings underscore that patients' interpretation about a certain behaviour might determine whether that behaviour is rated as desirable or aversive.


Assuntos
Dor , Parceiros Sexuais , Humanos , Pesquisa Qualitativa
13.
Clin J Pain ; 36(10): 750-756, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32769413

RESUMO

OBJECTIVES: Patients' pain behavior plays an important role in the interaction between patients and their partners, as acknowledged in operant models of pain. However, despite the considerable research attention to pain behaviors, the underlying motives of such behaviors are still unclear. The current study explores the motives to engage in pain behaviors and the possible discrepancies between individuals experiencing pain and partners' perceptions of those motives. METHODS: A qualitative study was performed, comprising semistructured interviews with 27 patients with chronic low back pain and their partners. They were recruited through purposive sampling at 2 pain clinics located in Tehran, Iran. RESULTS: Patients and partners mentioned a variety of motives for pain behaviors, including protecting oneself against more pain, regulating negative emotions, informing others about the pain severity, seeking validation or intimacy, gaining advantages from pain, and expressing anger. Patients and partners revealed the most similarities in motives such as protecting oneself against more pain and informing others about the pain severity. However, partners rarely acknowledged patients' motives for seeking validation and they were more likely to mention negative motives (eg, expressing anger). DISCUSSION: In conclusion, partners are more likely to attribute negative motives to the patient's pain behaviors, which may lead to their hostility toward patients. The findings of this study provide new insights into motives of pain behaviors from the perspective of patients and partners, which can inform couple-based interventions in terms of effective pain communication.


Assuntos
Motivação , Humanos , Irã (Geográfico) , Dor Lombar , Comportamento Sexual , Parceiros Sexuais
14.
G3 (Bethesda) ; 10(9): 3261-3269, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32690585

RESUMO

To better understand the evolution of virulence we are interested in identifying the genetic basis of this trait in pathogenic fungi and in developing tools for the rapid characterization of variation in virulence among populations associated with epidemics. Fusarium oxysporum f. sp. vasinfectum (FOV) is a haploid fungus that causes devastating outbreaks of Fusarium wilt of cotton wherever it is grown. In the United States, six nominal races and eleven genotypes of FOV have been characterized based on the translation elongation factor (EF-1α) gene and intergenic spacer region (IGS), but it is unclear how race or genotype based on these regions relates to population structure or virulence. We used genotyping-by-sequencing to identify SNPs and determine genetic diversity and population structure among 86 diverse FOV isolates. Six individuals of Fusarium oxysporum closely related to FOV were genotyped and included in some analyses. Between 193 and 354 SNPs were identified and included in the analyses depending on the pipeline and filtering criteria used. Phylogenetic trees, minimum spanning networks (MSNs), principal components analysis (PCA), and discriminant analysis of principal components (DAPC) demonstrated that races and genotypes of FOV are generally not structured by EF-1α genotype, nor are they monophyletic groups with the exception of race 4 isolates, which are distinct. Furthermore, DAPC identified between 11 and 14 genetically distinct clusters of FOV, whereas only eight EF-1α genotypes were represented among isolates; suggesting that FOV, especially isolates within the widely distributed and common race 1 genotype, is more genetically diverse than currently recognized.


Assuntos
Fusarium , Fusarium/genética , Variação Genética , Humanos , Filogenia , Doenças das Plantas
15.
Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165875, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32522631

RESUMO

Lysosomal storage disorders (LSDs) are diseases characterized by the accumulation of macromolecules in the late endocytic system and are caused by inherited defects in genes that encode mainly lysosomal enzymes or transmembrane lysosomal proteins. Niemann-Pick type C disease (NPCD), a LSD characterized by liver damage and progressive neurodegeneration that leads to early death, is caused by mutations in the genes encoding the NPC1 or NPC2 proteins. Both proteins are involved in the transport of cholesterol from the late endosomal compartment to the rest of the cell. Loss of function of these proteins causes primary cholesterol accumulation, and secondary accumulation of other lipids, such as sphingolipids, in lysosomes. Despite years of studying the genetic and molecular bases of NPCD and related-lysosomal disorders, the pathogenic mechanisms involved in these diseases are not fully understood. In this review we will summarize the pathogenic mechanisms described for NPCD and we will discuss their relevance for other LSDs with neurological components such as Niemann- Pick type A and Gaucher diseases. We will particularly focus on the activation of signaling pathways that may be common to these three pathologies with emphasis on how the intra-lysosomal accumulation of lipids leads to pathology, specifically to neurological impairments. We will show that although the primary lipid storage defect is different in these three LSDs, there is a similar secondary accumulation of metabolites and activation of signaling pathways that can lead to common pathogenic mechanisms. This analysis might help to delineate common pathological mechanisms and therapeutic targets for lysosomal storage diseases.


Assuntos
Doença de Gaucher/metabolismo , Metabolismo dos Lipídeos/genética , Lisossomos/patologia , Doença de Niemann-Pick Tipo A/metabolismo , Doença de Niemann-Pick Tipo C/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/patologia , Colesterol/metabolismo , Doença de Gaucher/genética , Doença de Gaucher/patologia , Glucosilceramidase/genética , Glucosilceramidase/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisossomos/metabolismo , Mutação , Neurônios/citologia , Neurônios/metabolismo , Neurônios/patologia , Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo A/genética , Doença de Niemann-Pick Tipo A/patologia , Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/patologia , Transdução de Sinais/genética , Esfingolipídeos/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
16.
PeerJ ; 7: e7986, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799067

RESUMO

Uromyces transversalis, the causal agent of Gladiolus rust, is an invasive plant pathogen in the United States and is regulated as a quarantine pathogen in Europe. The aim of this research was to: (i) determine the origin of introductions of U. transversalis to the United States, (ii) track the movement of genotypes, and (iii) understand the worldwide genetic diversity of the species. To develop molecular markers for genotyping, whole genome sequencing was performed on three isolates collected in the United States. Genomes were assembled de novo and searched for microsatellite regions. Primers were developed and tested on ten isolates from the United States resulting in the identification of 24 polymorphic markers. Among 92 isolates collected from Costa Rica, Mexico, New Zealand, Australia, and the United States there were polymorphisms within isolates with no genotypic diversity detected among isolates; however, missing data among the New Zealand and Australia isolates due to either poor amplification of degraded DNA or null alleles as a result of genetic differences made it difficult to generate conclusions about these populations. The microsatellite loci and flanking regions showed high diversity and two divergent genomes within dikaryotic individuals, yet no diversity among individuals, suggesting that the invasive U. transversalis populations from North America are strictly clonal.

17.
BMC Public Health ; 19(1): 994, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340786

RESUMO

BACKGROUND: Homelessness is increasing globally. It results in poorer physical and mental health than age matched people living in permanent housing. Better information on the health needs of people experiencing homelessness is needed to inform effective resourcing, planning and service delivery by government and care organisations. The aim of this review was to identify assessment tools that are valid, reliable and appropriate to measure the health status of people who are homeless. METHODS: Data sources: A systematic literature search was conducted in PubMed (and Medline), PsychInfo, Scopus, CINAHL and ERIC from database inception until September 2018. Key words used were homeless, homelessness, homeless persons, vagrancy, health status, health, health issues, health assessment and health screening. The protocol was registered with PROSPERO. The National Health and Medical Research Council of Australia (NHMRC) hierarchy of evidence was applied; methodological quality of included articles was assessed using the McMaster critical appraisal tools and psychometric properties of the tools were appraised using the International Centre for Allied Health Evidence Ready Reckoner. RESULTS: Diverse tools and measures (N = 71) were administered within, and across the reviewed studies (N = 37), with the main focus being on general health, oral health and nutrition. Eleven assessment tools in 13 studies had evidence of appropriate psychometric testing for the target population in domains of quality of life and health status, injury, substance use, mental health, psychological and cognitive function. Methodological quality of articles and tools were assessed as moderate to good. No validated tools were identified to assess oral health, chronic conditions, anthropometry, demography, nutrition, continence, functional decline and frailty, or vision and hearing. However, assessments of physical constructs (such as oral health, anthropometry, vision and hearing) could be applied to homeless people on a presumption of validity, because the constructs would be measured with clinical indicators in the same manner as people living in permanent dwellings. CONCLUSIONS: This review highlighted the need to develop consistent and comprehensive health assessment tools validated with, and tailored for, adults experiencing homelessness.


Assuntos
Programas de Triagem Diagnóstica , Pessoas Mal Alojadas/psicologia , Programas de Rastreamento/métodos , Adulto , Austrália , Feminino , Nível de Saúde , Indicadores Básicos de Saúde , Humanos , Masculino , Psicometria , Adulto Jovem
18.
Plant Dis ; 103(9): 2271-2276, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31287371

RESUMO

Sensitivity monitoring of Venturia effusa, cause of pecan scab, has revealed insensitivity to fentin hydroxide and tebuconazole, but recent research indicates that the insensitivity to fentin hydroxide is not stable. A study was undertaken to determine if a fitness cost may be responsible for this instability. In this study, experiments were conducted to evaluate fitness components and phenotypic stability of insensitivity of V. effusa to fentin hydroxide and tebuconazole. Conidial production, conidial germination, microcolony growth, sensitivity to osmotic stress, and sensitivity to oxidative stress in the absence of fungicide were compared for isolates with differing sensitivities to both fungicides. Percent conidial germination decreased linearly with increasing fentin hydroxide insensitivity, and microcolony growth on 1.0 mM H2O2 decreased linearly with increasing tebuconazole insensitivity. Stability of resistance was assessed on concentrations of 1.0, 3.0, and 10 µg/ml of both fungicides prior to and after five transfers on non-fungicide-amended medium. Tebuconazole insensitivity was stable after transfers, but fentin hydroxide insensitivity on 1.0 and 3.0 µg/ml decreased significantly after transfers, indicating instability. Here we provide evidence that in V. effusa tebuconazole insensitivity is stable and fentin hydroxide insensitivity is not. These results suggest that fentin-hydroxide-resistant V. effusa isolates have reduced conidial viability compared with sensitive isolates, which may allow the population to regain sensitivity in the absence of this frequently used fungicide.


Assuntos
Ascomicetos , Farmacorresistência Fúngica , Compostos Orgânicos de Estanho , Triazóis , Ascomicetos/efeitos dos fármacos , Compostos Orgânicos de Estanho/farmacologia , Triazóis/farmacologia
19.
J Nematol ; 51: 1-10, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31088027

RESUMO

The interaction between Fusarium oxysporum f. sp. vasinfectum (Fov) and Meloidogyne incognita (root-knot nematode) resulting in Fusarium wilt (FW) of cotton is well-known. Although Belonolaimus longicaudatus (sting nematode) can also interact with Fov and cause FW, it has long been believed that virtually all of the FW in Georgia is caused by the interaction of Fov with M. incognita. In recent years, FW has been reported more frequently in Georgia, which suggests that something affecting the disease complex may have changed. In 2015 and 2016, a survey of 27 Georgia cotton fields in 10 counties was conducted. At least 10 soil and stem samples per field were collected from individual plants showing symptoms of FW to quantify plant-parasitic nematode levels and identify Fov races. Fov race 1 was identified in all samples in 2015, but one sample also had the LA110 genotype and another sample also had the LA108 genotype. In 2016, all Fov races and genotypes found in 2015 were present, however, MDS-12 and LA127/140 also were found. Meloidogyne incognita was present in 18% of fields in 2015 and 40% in 2016, whereas B. longicaudatus was present in all fields in 2015 and 75% of fields in 2016. Regardless of whether they occurred separately or together, M. incognita and B. longicaudatus were present, respectively, in 18% and 55% of individual samples in 2015 and 40% and 51% in 2016. However, M. incognita without B. longicaudatus was found in 7% of samples in 2015 and 34% in 2016, whereas B. longicaudatus without M. incognita was found in 45% of samples in 2015 and 44% in 2016. We conclude that Fov race 1 continues to be the dominant race in Georgia and many instances of FW in Georgia may be due to Fov interacting with B. longicaudatus and not M. incognita as previously believed.The interaction between Fusarium oxysporum f. sp. vasinfectum (Fov) and Meloidogyne incognita (root-knot nematode) resulting in Fusarium wilt (FW) of cotton is well-known. Although Belonolaimus longicaudatus (sting nematode) can also interact with Fov and cause FW, it has long been believed that virtually all of the FW in Georgia is caused by the interaction of Fov with M. incognita. In recent years, FW has been reported more frequently in Georgia, which suggests that something affecting the disease complex may have changed. In 2015 and 2016, a survey of 27 Georgia cotton fields in 10 counties was conducted. At least 10 soil and stem samples per field were collected from individual plants showing symptoms of FW to quantify plant-parasitic nematode levels and identify Fov races. Fov race 1 was identified in all samples in 2015, but one sample also had the LA110 genotype and another sample also had the LA108 genotype. In 2016, all Fov races and genotypes found in 2015 were present, however, MDS­12 and LA127/140 also were found. Meloidogyne incognita was present in 18% of fields in 2015 and 40% in 2016, whereas B. longicaudatus was present in all fields in 2015 and 75% of fields in 2016. Regardless of whether they occurred separately or together, M. incognita and B. longicaudatus were present, respectively, in 18% and 55% of individual samples in 2015 and 40% and 51% in 2016. However, M. incognita without B. longicaudatus was found in 7% of samples in 2015 and 34% in 2016, whereas B. longicaudatus without M. incognita was found in 45% of samples in 2015 and 44% in 2016. We conclude that Fov race 1 continues to be the dominant race in Georgia and many instances of FW in Georgia may be due to Fov interacting with B. longicaudatus and not M. incognita as previously believed.

20.
Pest Manag Sci ; 75(11): 3093-3101, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30924240

RESUMO

BACKGROUND: Gummy stem blight (GSB) is a devastating disease of cucurbits that has been effectively managed with fungicide applications. However, the Stagonosporopsis spp. that cause GSB have rapidly evolved resistance to multiple classes of fungicides. To better understand the evolution and persistence of fungicide resistance in field populations, resistance profiles of unique and clonal genotypes of 113 Stagonosporopsis citrulli and 19 S. caricae isolates to four different fungicides were determined based on in vitro mycelial growth assays and molecular markers based on genes encoding fungicide targets. RESULTS: All 19 S. caricae isolates screened were resistant to tebuconazole and azoxystrobin, and sensitive to boscalid and fluopyram. All 113 S. citrulli isolates were sensitive to tebuconazole and sensitive to fluopyram, with one exception that was fluopyram-resistant. All isolates of S. citrulli except two were resistant to azoxystrobin. Phenotypic differences in response to boscalid were detected among S. citrulli isolates, but the phenotypes were not associated with multilocus genotypes (MLG) determined by 16 microsatellite loci. Additionally, isolates sharing the same MLG varied by SdhB genotype. A unique mutation of I229V in SdhB, a target of succinate dehydrogenase inhibitor fungicides, was detected for the fluopyram-resistant isolate of S. citrulli. CONCLUSION: Both the lack of association of fungicide resistance profiles with genetic similarity of isolates based on microsatellite loci and the finding that widely distributed MLG varied in fungicide resistance profiles suggest that independent evolutionary events for resistance to boscalid have likely occurred. Frequent genetic recombination within populations may be responsible for resistance to multiple fungicides. This study provides useful information for effectively managing both species of GSB fungi present in the southeastern USA and understanding the evolution of fungicide resistance within populations of plant-pathogenic fungi. © 2019 Society of Chemical Industry.


Assuntos
Ascomicetos/efeitos dos fármacos , Farmacorresistência Fúngica , Fungicidas Industriais/farmacologia , Doenças das Plantas/prevenção & controle , Estrobilurinas/farmacologia , Succinato Desidrogenase/antagonistas & inibidores , Ascomicetos/fisiologia , Citrullus/microbiologia , Desmetilação/efeitos dos fármacos , Florida , Georgia , Doenças das Plantas/microbiologia , Especificidade da Espécie
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