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Kashif Mehmood Michael P. Wilczek Jeanne K. DuShane Matthew T. Parent Colleen L. Mayberry Jaqulin N. Wallace Francois L. Levasseur Tristan M. Fong Samuel T. Hess Melissa S. Maginnis 《Viruses》2022,14(12)
The organization and dynamics of plasma membrane receptors are a critical link in virus-receptor interactions, which finetune signaling efficiency and determine cellular responses during infection. Characterizing the mechanisms responsible for the active rearrangement and clustering of receptors may aid in developing novel strategies for the therapeutic treatment of viruses. Virus-receptor interactions are poorly understood at the nanoscale, yet they present an attractive target for the design of drugs and for the illumination of viral infection and pathogenesis. This study utilizes super-resolution microscopy and related techniques, which surpass traditional microscopy resolution limitations, to provide both a spatial and temporal assessment of the interactions of human JC polyomavirus (JCPyV) with 5-hydroxytrypamine 2 receptors (5-HT2Rs) subtypes during viral entry. JCPyV causes asymptomatic kidney infection in the majority of the population and can cause fatal brain disease, and progressive multifocal leukoencephalopathy (PML), in immunocompromised individuals. Using Fluorescence Photoactivation Localization Microscopy (FPALM), the colocalization of JCPyV with 5-HT2 receptor subtypes (5-HT2A, 5-HT2B, and 5-HT2C) during viral attachment and viral entry was analyzed. JCPyV was found to significantly enhance the clustering of 5-HT2 receptors during entry. Cluster analysis of infected cells reveals changes in 5-HT2 receptor cluster attributes, and radial distribution function (RDF) analyses suggest a significant increase in the aggregation of JCPyV particles colocalized with 5-HT2 receptor clusters in JCPyV-infected samples. These findings provide novel insights into receptor patterning during viral entry and highlight improved technologies for the future development of therapies for JCPyV infection as well as therapies for diseases involving 5-HT2 receptors. 相似文献
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Geographic differences in manifestation of psoriatic arthritis (PsA) could be related to differences in genetic or environmental factors. We aimed to compare the disease activity and functional status using validated outcome measures among patients with PsA of different ethnicities living in the same environment. We performed a cross-sectional study on consecutive patients with PsA classified by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria from a single center. Sociodemographic data, clinical variables, and patient-reported outcomes were collected using a standardized protocol. Disease activities were assessed by validated composite scores: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), Composite Psoriatic Disease Activity Index (CPDAI), and minimal disease activity (MDA). Physical function was assessed with Health Assessment Questionnaire (HAQ) and the Medical Outcome Study Short-Form 36 (SF36) physical function subscales. Linear regression analyses were performed to identify variables associated with disease activities and physical function. Ninety-eight patients (51.5%, men) with mean (±SD) age and duration of PsA of 51.5 ± 13.8 and 5.5 ± 8.4 years were recruited. Indian was overrepresented compared with the national distribution of ethnicities. Compared to Chinese, Indian patients were more likely to be using biological therapies, have higher tender joint count, and worse enthesitis. Higher proportion of Indians had higher disease activity categories measured by cDAPSA, CPDAI, and MDA and had poorer physical function. In the multivariable analysis, ethnicity was significantly associated with HAQ and SF36-PF. Compared to Chinese, Indians with PsA living in the same environment had worse disease activity and physical function measured by validated outcomes. 相似文献
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V. Sawlani N. Davies M. Patel R. Flintham C. Fong G. Heyes G. Cruickshank N. Steven A. Peet A. Hartley H. Benghiat S. Meade P. Sanghera 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(1):41-49
Aims
Following stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question.Materials and methods
Multiparametric MRI techniques, including spectroscopy, diffusion and perfusion imaging, were used for the differentiation of radiation-related changes and tumour recurrence after SRS for intracranial metastases in six cases. All patients presented with enlargement of the treated lesion, an increase in perilesional brain oedema and aggravation or appearance of neurological signs and symptoms from 7 to 29 weeks after primary treatment.Results
Multiparametric imaging helped to differentiate features of tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent diffusion coefficient (ADC) <1000 × 10?6 mm2/s, high relative cerebral blood volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested tumour recurrence. A high ADC > 1000 × 10?6 mm2/s, low rCBV ratio < 2.1, Cho:Cr ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI diagnosis was confirmed by histology or radiological and clinical follow-up.Conclusion
Multiparametric MRI was helpful in the early identification of radiation-related changes and tumour recurrence and may be useful for monitoring treatment changes in intracranial neoplasms after SRS treatment. 相似文献87.
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Liver stiffness measurement predicts high‐grade post‐hepatectomy liver failure: A prospective cohort study 下载免费PDF全文
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A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies requires a thorough understanding of the underlying mechanisms of malignant transformation driven by aberrant epigenetic regulators. In this review we provide an overview of the major protagonists in epigenetic regulation, their aberrant role in myeloid malignancies, prognostic significance and potential for therapeutic targeting. 相似文献
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