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BACKGROUND: The processes that shape microbial biogeography are not well understood, and concepts that apply to macroorganisms, like dispersal barriers, may not affect microorganisms in the same predictable ways. To better understand how known macro-scale biogeographic processes can be applied at micro-scales, we examined seagrass associated microbiota on either side of Wallace's line to determine the influence of this cryptic dispersal boundary on the community structure of microorganisms. Communities were examined from twelve locations throughout Indonesia on either side of this theoretical line. RESULTS: We found significant differences in microbial community structure on either side of this boundary (R2 = 0.09; P = 0.001), and identified seven microbial genera as differentially abundant on either side of the line, six of these were more abundant in the West, with the other more strongly associated with the East. Genera found to be differentially abundant had significantly smaller minimum cell dimensions (GLM: t923 = 59.50, P < 0.001) than the overall community. CONCLUSION: Despite the assumed excellent dispersal ability of microbes, we were able to detect significant differences in community structure on either side of this cryptic biogeographic boundary. Samples from the two closest islands on opposite sides of the line, Bali and Komodo, were more different from each other than either was to its most distant island on the same side. We suggest that limited dispersal across this barrier coupled with habitat differences are primarily responsible for the patterns observed. The cryptic processes that drive macroorganism community divergence across this region may also play a role in the bigeographic patterns of microbiota.
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BACKGROUND: Microbes have fundamental roles underpinning the functioning of our planet, they are involved in global carbon and nutrient cycling, and support the existence of multicellular life. The mangrove ecosystem is nutrient limited and if not for microbial cycling of nutrients, life in this harsh environment would likely not exist. The mangroves of Southeast Asia are the oldest and most biodiverse on the planet, and serve vital roles helping to prevent shoreline erosion, act as nursery grounds for many marine species and sequester carbon. Despite these recognised benefits and the importance of microbes in these ecosystems, studies examining the mangrove microbiome in Southeast Asia are scarce.cxs RESULTS: Here we examine the microbiome of Avicenia alba and Sonneratia alba and identify a core microbiome of 81 taxa. A further eight taxa (Pleurocapsa, Tunicatimonas, Halomonas, Marinomonas, Rubrivirga, Altererythrobacte, Lewinella, and Erythrobacter) were found to be significantly enriched in mangrove tree compartments suggesting key roles in this microbiome. The majority of those identified are involved in nutrient cycling or have roles in the production of compounds that promote host survival. CONCLUSION: The identification of a core microbiome furthers our understanding of mangrove microbial biodiversity, particularly in Southeast Asia where studies such as this are rare. The identification of significantly different microbial communities between sampling sites suggests environmental filtering is occurring, with hosts selecting for a microbial consortia most suitable for survival in their immediate environment. As climate change advances, many of these microbial communities are predicted to change, however, without knowing what is currently there, it is impossible to determine the magnitude of any deviations. This work provides an important baseline against which change in microbial community can be measured.
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An exponential rise in the use of cross-sectional imaging has led to an increase in the incidental identification of pancreatic cystic lesions (PCL); however, with many subtypes defined to date and heterogeneous morphology with often absent defining radiological features, PCLs present a diagnostic challenge. Computed tomography (CT) and/or magnetic resonance imaging (MRI) alone are frequently not sufficient to provide accurate characterisation. Endoscopic ultrasound (EUS) has an important role in the evaluation and classification of PCLs through its ability to define the internal architecture, which is further enhanced by the use of contrast medium. It is also used widely for the surveillance of larger cysts (>2 cm), which are associated with a greater malignant potential. The aim of this review is to demonstrate the role of contrast-enhanced (CE)-EUS in the diagnosis and risk stratification of PCLs. The features of the main non-neoplastic and neoplastic PCLs observed on CE-EUS are provided. When used in combination with other imaging techniques and patient characteristics, CE-EUS offers a more accurate assessment of PCLs and aids risk stratification. Additionally, CE-EUS enables assessment of parenchymal perfusion improving the precision of cyst characterisation and targeted biopsy of worrisome components. The International Consensus Guidelines recommend regular follow up for patients with mucinous or indeterminate PCLs that are fit enough for surgery. With the growing range of tools available to assess PCLs including CE-EUS, it is hoped that patients can be steered towards surgery, surveillance, or discharge with increasing accuracy.
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Cisto Pancreático , Neoplasias Pancreáticas , Endossonografia , Humanos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios XRESUMO
In the beginning of the COVID-19 pandemic, there were major concerns regarding the huge demand for asthma inhalers. Using the primary-care medical records for 614,700 asthma patients between January and June 2020, we found that there was a substantial increase in inhalers solely in March 2020. Patients significantly associated with receiving higher inhaled corticosteroid prescriptions were younger, of higher socioeconomic status, and had milder asthma.
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Asma , COVID-19 , Administração por Inalação , Asma/tratamento farmacológico , Humanos , Nebulizadores e Vaporizadores , Pandemias , Prescrições , SARS-CoV-2RESUMO
Intraductal papillary mucinous neoplasm of the bile duct is a rare tumour only recently classified as a distinct pathological entity. These neoplasms, rarely encountered in clinical practice in the UK, are now considered to be important precursors for the development of cholangiocarcinoma. We present a histologically confirmed case of intraductal papillary neoplasm of the bile duct in a male patient and discuss the main radiographic manifestations of this rare condition across multiple imaging modalities, with an emphasis on the imaging features of endoscopic ultrasonography and its role in establishing the diagnosis.
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Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Papilar/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Endossonografia , Cuidados Pré-Operatórios/métodos , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Papilar/patologia , Adenocarcinoma Papilar/cirurgia , Idoso , Variação Anatômica , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/anormalidades , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Hepatectomia/métodos , Humanos , Achados Incidentais , Masculino , Tomografia Computadorizada por Raios X , Resultado do TratamentoAssuntos
COVID-19 , Pandemias , Tomada de Decisão Clínica , Humanos , Cidade de Nova Iorque , SARS-CoV-2RESUMO
Short half-life proteins regulate many essential processes, including cell cycle, transcription, and apoptosis. However, few well-characterized protein-turnover pathways have been identified because traditional methods to measure protein half-life are time and labor intensive. To overcome this barrier, we developed a protein stability probe and high-content screening pipeline for novel regulators of short half-life proteins using automated image analysis. Our pilot probe consists of the short half-life protein c-MYC (MYC) fused to Venus fluorescent protein (MYC-Venus). This probe enables protein half-life to be scored as a function of fluorescence intensity and distribution. Rapid turnover prevents maximal fluorescence of the probe due to the relatively longer maturation time of the fluorescent protein. Cells expressing the MYC-Venus probe were analyzed using a pipeline in which automated confocal microscopy and image analyses were used to score MYC-Venus stability by two strategies: assaying the percentage of cells with Venus fluorescence above background, and phenotypic comparative analysis. To evaluate this high-content screening pipeline and our probe, a kinase inhibitor library was screened by confocal microscopy to identify known and novel kinases that regulate MYC stability. Compounds identified were shown to increase the half-life of both MYC-Venus and endogenous MYC, validating the probe and pipeline. Fusion of another short half-life protein, myeloid cell leukemia 1 (MCL1), with Venus also demonstrated an increase in percent Venus-positive cells after treatment with inhibitors known to stabilize MCL1. Together, the results validate the use of our automated microscopy and image analysis pipeline of stability probe-expressing cells to rapidly and quantitatively identify regulators of short half-life proteins. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
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Apoptose , Proteínas , Humanos , Microscopia Confocal , Microscopia de Fluorescência , Estabilidade ProteicaRESUMO
Intestinal failure is the inability to maintain adequate nutrition or hydration through the gut. It is caused by a diverse range of benign and malignant aetiologies. Imaging takes a central role in the multidisciplinary assessment of patients with intestinal failure.
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Diagnóstico por Imagem/métodos , Enteropatias/diagnóstico por imagem , Adulto , Humanos , Intestinos/diagnóstico por imagemRESUMO
Intestinal transplant is considered in a small number of patients with intestinal failure or locally invasive benign abdominal tumours to improve both quality of life and survival. The complexity of the underlying diseases and postoperative findings are reflected in the imaging undertaken to support this patient group. Increasing numbers of patients are undergoing these procedures. Radiologists are increasingly likely to encounter these patients before and after surgery. This article will discuss the imaging findings that may prompt referral for transplantation assessment. It will also describe surgical anatomy and postoperative complications.
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Diagnóstico por Imagem/métodos , Enteropatias/diagnóstico por imagem , Enteropatias/cirurgia , Intestinos/diagnóstico por imagem , Intestinos/transplante , Rejeição de Enxerto/diagnóstico por imagem , Humanos , Complicações Pós-Operatórias/diagnóstico por imagemRESUMO
The Myc oncoprotein is a key contributor to the development of many human cancers. As such, understanding its molecular activities and biological functions has been a field of active research since its discovery more than three decades ago. Genome-wide studies have revealed Myc to be a global regulator of gene expression. The identification of its DNA-binding partner protein, Max, launched an area of extensive research into both the protein-protein interactions and protein structure of Myc. In this review, we highlight key insights with respect to Myc interactors and protein structure that contribute to the understanding of Myc's roles in transcriptional regulation and cancer. Structural analyses of Myc show many critical regions with transient structures that mediate protein interactions and biological functions. Interactors, such as Max, TRRAP, and PTEF-b, provide mechanistic insight into Myc's transcriptional activities, while others, such as ubiquitin ligases, regulate the Myc protein itself. It is appreciated that Myc possesses a large interactome, yet the functional relevance of many interactors remains unknown. Here, we discuss future research trends that embrace advances in genome-wide and proteome-wide approaches to systematically elucidate mechanisms of Myc action. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.
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Neoplasias/genética , Mapas de Interação de Proteínas/genética , Proteoma , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Regulação da Expressão Gênica , Genoma Humano , Humanos , Neoplasias/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Conformação Proteica , Processamento de Proteína Pós-Traducional/genética , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteínas Proto-Oncogênicas c-myc/metabolismoRESUMO
We aimed to evaluate the attitudes and knowledge of medical students' towards surrogacy as a means of assisted reproduction. An online survey was sent to medical students from UK universities, 185 anonymous replies were received. A total of 72.2% agreed with surrogacy as a means of assisted reproduction; 43.9% thought the intended mother was the legal mother at birth; 28.7% correctly identified the surrogate mother as the legal mother; 76.0%felt that the intended mother should be the legal mother at birth; 15.2% thought surrogacy arrangements were enforceable by law; 29.2% correctly knew they were not. There was no difference in knowledge of surrogacy among students who had studied obstetrics and gynaecology compared with those who had not. Medical students were generally tolerant in their attitudes to surrogacy. There were discrepancies between the position of UK law governing surrogacy and the personal views of medical students.
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Conhecimentos, Atitudes e Prática em Saúde , Técnicas de Reprodução Assistida/psicologia , Estudantes de Medicina/psicologia , Mães Substitutas , Feminino , Humanos , Gravidez , Técnicas de Reprodução Assistida/legislação & jurisprudência , Reino Unido , Adulto JovemRESUMO
The most commonly used animal model for the study of HIV-1 infection in humans is the infection of non-human primates by simian immunodeficiency virus (SIV). The animal hosts used most frequently are different species of macaques, which are readily infected with SIV, and can therefore be used to study natural infection, pathogenesis, therapy, and vaccine efficacy. The study of HIV-1 infection in humans relies heavily on the quantification of HIV-1 load (i.e. viral RNA) in patient plasma. Given the importance of HIV-1 RNA levels in humans, it follows that SIV RNA levels in animals are also relevant to the study of infection in this model system. This report describes the development of the isothermal amplification-based NASBA technology for the quantification of SIV RNA load in macaque plasma. Evaluation of the assay using model systems demonstrated that the assay is accurate and reproducible over nearly four orders of magnitude. Viral RNA load data were compared to other infection measurements in the macaque system. Further, the assay was used to provide copy number levels of SIV RNA in macaque plasma samples, permitting characterization of viral load during the course of SIV infection.
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Técnicas de Amplificação de Ácido Nucleico , RNA Viral/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia , Carga Viral , Animais , Contagem de Linfócito CD4 , Estudos de Avaliação como Assunto , Macaca mulatta , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Síndrome de Imunodeficiência Adquirida dos Símios/diagnóstico , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/isolamento & purificaçãoRESUMO
Undergraduate students completed a series of training tasks consisting of solving anagrams, performing addition problems, and making perceptual discriminations, to validate findings of learned industriousness. The group that received high-effort training was given difficult and demanding tasks, whereas the group that received low-effort training was given easy tasks. Controls were given no preliminary training activity. For the criterion task, all participants were provided with a series of pencil and paper mazes to complete. They were allowed to "pass" on whatever mazes they wished (they could progress to the next maze but could not return to any that had been passed). Participants who had received high-effort training passed on significantly fewer mazes than did those in the control and low-effort conditions, thus supporting the generality of effects of reinforced high effort.
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Aprendizagem , Trabalho , HumanosRESUMO
African American women are less likely than white women to receive and perform adequate breast screening, and represent a group that has not been thoroughly researched in the area of breast cancer risk. In general, perceptions of risk and worry about cancer are both related to obtaining mammography and possibly other screening activities. We examine African American women's worry and beliefs about breast cancer, and their intentions to perform breast and genetic screening behaviors, using the self-regulatory model. Participants were recruited via media announcements; they completed questionnaires addressing several aspects of the self-regulatory model. Forty-one percent of participants were underestimators, 23% were overestimators, and 37% were extreme overestimators of their own personal risk for breast cancer. Several variables were significant predictors of willingness to undergo mammography and genetic screening, including ethnic identity, attitudes toward the physician, emotional distress, and risk overestimation. These data highlight the importance of psychological variables in understanding screening in African American women and hold promise for intervention design.
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Atitude Frente a Saúde/etnologia , Negro ou Afro-Americano/psicologia , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/psicologia , Programas de Rastreamento/psicologia , Saúde da Mulher , Adulto , Idoso , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Estudos de AmostragemRESUMO
We present experimental evidence of the dependence of coating scatter on a substrate preparation technique for fused silica substrates. Samples included conventionally polished, superpolished, andfloat-polished substrates. We used scatterometry and total internal reflection microscopy to investigate the effects of substrate preparation on the performance of zirconium oxide thin films. Results indicate that scatter from coatings dominates the scatter signature of the coated optic. They also demonstrate that substrate preparation can affect the level of scatter produced in optical coatings. In addition it is observed that the substrates with the lowest scatter do not necessarily result in the coatings with the lowest scatter.
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The recombinant gene for hepatitis B core antigen (HBcAg) was cloned and expressed, and the protein was purified from Escherichia coli cultures. Purified HBcAg was tested for the effects of various physical and chemical agents on its immunoreactivity by a paramagnetic particle-based enzyme immunoassay. Recombinant HBcAg retained its immunoreactivity when heated at 70 degrees C for 60 min but was inactivated at 85 degrees C in 10 min. It was stable between pHs 5 and 10.5 but not at pHs 2 and 13.5. Treatment with sodium dodecyl sulfate (SDS), ethanol, and methanol caused a significant loss in HBcAg reactivity. The proteolytic enzymes papain and bacterial protease (type VIII from Bacillus licheniformis) degraded HBcAg significantly, but trypsin and chymotrypsin did not. The effect of combined SDS and 2-mercaptoethanol on recombinant HBcAg was an immediate loss in immunoreactivity, followed by rapid recovery to about 50% of the initial level. This level was maintained for 24 to 48 h and was followed by an almost total loss of HBcAg in about 120 h.
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Antígenos do Núcleo do Vírus da Hepatite B/química , Sequência de Bases , Etanol , Temperatura Alta , Concentração de Íons de Hidrogênio , Técnicas Imunoenzimáticas , Metanol , Dados de Sequência Molecular , Peptídeo Hidrolases , Proteínas Recombinantes/químicaRESUMO
We have isolated a quail cardiac tropomyosin gene which encodes three distinct isoforms through the use of alternative exon splicing. Characterization of cDNA clones produced by this gene indicate that the gene encodes a unique 284 amino acid cardiac tropomyosin isoform, along with a 248 amino acid cytoskeletal and 284 amino acid smooth muscle isoforms. Northern analyses indicate that the gene is primarily expressed in cardiac muscle, with only minor expression of the cytoskeletal and smooth muscle transcripts.