73 research outputs found

    Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability.

    Get PDF
    Monocytes play a central role in regulating inflammation in response to infection or injury, and during auto-inflammatory diseases. Human blood contains classical, intermediate and non-classical monocyte subsets that each express characteristic patterns of cell surface CD16 and CD14; each subset also has specific functional properties, but the mechanisms underlying many of their distinctive features are undefined. Of particular interest is how monocyte subsets regulate secretion of the apical pro-inflammatory cytokine IL-1β, which is central to the initiation of immune responses but is also implicated in the pathology of various auto-immune/auto-inflammatory conditions. Here we show that primary human non-classical monocytes, exposed to LPS or LPS + BzATP (3'-O-(4-benzoyl)benzyl-ATP, a P2X7R agonist), produce approx. 80% less IL-1β than intermediate or classical monocytes. Despite their low CD14 expression, LPS-sensing, caspase-1 activation and P2X7R activity were comparable in non-classical monocytes to other subsets: their diminished ability to produce IL-1β instead arose from 50% increased IL-1β mRNA decay rates, mediated by Hsp27. These findings identify the Hsp27 pathway as a novel therapeutic target for the management of conditions featuring dysregulated IL-1β production, and represent an advancement in understanding of both physiological inflammatory responses and the pathogenesis of inflammatory diseases involving monocyte-derived IL-1β

    A Modified Protocol for Bisulfite Genomic Sequencing of Difficult Samples

    Get PDF
    The bisulfite genomic sequencing protocol is a widely used method for analyzing DNA methylation. It relies on the deamination of unmethylated cytosine residues to uracil; however, its high rates of DNA degradation and incomplete cytosine to uracil conversion often lead to failed experiments, uninformative results, and false positives. Here, we report the addition of a single-step multiple restriction enzyme digestion (MRED) designed to differentially digest polymerase chain reaction products amplified from unconverted DNA while leaving those of converted DNA intact. We show that for our model system, RARB2 P2 promoter, use of MRED increased informative sequencings ninefold, and MRED did not alter the clonal representation in one fully methylated cell line, H-596, treated or not with 5-azadeoxycytidine, a methylation inhibitor. We believe that this method may easily be adapted for analyzing other genes and provide guidelines for selecting the most appropriate MRED restriction enzymes

    Microplastic-Associated Biofilms: A Comparison of Freshwater and Marine Environments

    Get PDF
    Microplastics (<5 mm particles) occur within both engineered and natural freshwater ecosystems, including wastewater treatment plants, lakes, rivers, and estuaries. While a significant proportion of microplastic pollution is likely sequestered within freshwater environments, these habitats also constitute an important conduit of microscopic polymer particles to oceans worldwide. The quantity of aquatic microplastic waste is predicted to dramatically increase over the next decade, but the fate and biological implications of this pollution are still poorly understood. A growing body of research has aimed to characterize the formation, composition, and spatiotemporal distribution of microplastic-associated (“plastisphere”) microbial biofilms. Plastisphere microorganisms have been suggested to play significant roles in pathogen transfer, modulation of particle buoyancy, and biodegradation of plastic polymers and co-contaminants, yet investigation of these topics within freshwater environments is at a very early stage. Here, what is known about marine plastisphere assemblages is systematically compared with up-to-date findings from freshwater habitats. Through analysis of key differences and likely commonalities between environments, we discuss how an integrated view of these fields of research will enhance our knowledge of the complex behavior and ecological impacts of microplastic pollutants

    Ethical framework of assistive devices: review and reflection

    Get PDF
    The population of ageing is growing significantly over the world, and there is an emerging demand for better healthcare services and more care centres. Innovations of Information and Communication Technology has resulted in development of various types of assistive robots to fulfil elderly’s needs and independency, whilst carrying out daily routine tasks. This makes it vital to have a clear understanding of elderly’s needs and expectations from assistive robots. This paper addresses current ethical issues to understand elderly’s prime needs. Also, we consider other general ethics with the purpose of applying these theories to form a proper ethics framework. In the ethics framework, the ethical concerns of senior citizens will be prioritized to satisfy elderly’s needs and also to diminish related expenses to healthcare services

    Microseismic Full Waveform Modeling in Anisotropic Media with Moment Tensor Implementation

    Get PDF
    Seismic anisotropy which is common in shale and fractured rocks will cause travel-time and amplitude discrepancy in different propagation directions. For microseismic monitoring which is often implemented in shale or fractured rocks, seismic anisotropy needs to be carefully accounted for in source location and mechanism determination. We have developed an efficient finite-difference full waveform modeling tool with an arbitrary moment tensor source. The modeling tool is suitable for simulating wave propagation in anisotropic media for microseismic monitoring. As both dislocation and non-double-couple source are often observed in microseismic monitoring, an arbitrary moment tensor source is implemented in our forward modeling tool. The increments of shear stress are equally distributed on the staggered grid to implement an accurate and symmetric moment tensor source. Our modeling tool provides an efficient way to obtain the Green’s function in anisotropic media, which is the key of anisotropic moment tensor inversion and source mechanism characterization in microseismic monitoring. In our research, wavefields in anisotropic media have been carefully simulated and analyzed in both surface array and downhole array. The variation characteristics of travel-time and amplitude of direct P- and S-wave in vertical transverse isotropic media and horizontal transverse isotropic media are distinct, thus providing a feasible way to distinguish and identify the anisotropic type of the subsurface. Analyzing the travel-times and amplitudes of the microseismic data is a feasible way to estimate the orientation and density of the induced cracks in hydraulic fracturing. Our anisotropic modeling tool can be used to generate and analyze microseismic full wavefield with full moment tensor source in anisotropic media, which can help promote the anisotropic interpretation and inversion of field data

    Genomic reconstruction of the SARS-CoV-2 epidemic in England.

    Get PDF
    The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021

    OBESITY AND ITS ASSOCIATION WITH OTHER CARDIOVASCULAR RISK FACTORS IN WOMEN IN CENTRAL IRAN - WOMEN'S HEALTHY HEART PROJECT

    No full text
    Abstract&nbsp; INTRODUCTION: Cardiovascular diseases (CVD) are considered the most important cause of death worldwide. Obesity is a major CVD risk factor. This study was conducted to evaluate the prevalence of obesity and its association with other CVD risk factors in Iranian women. methods: This cross-sectional study was conducted in 2001 as part of Isfahan Healthy Heart Program (IHHP) in three Central Iranian cities of Isfahan, Najaf-Abad and Arak. Being over 19 years of age, absence of pregnancy, absence of mental retardation and Iranian nationality were the criteria for inclusion in the study. A questionnaire on demographics characteristics, drug consumption, smoking status, and physical activity were filled out for every subject. Height, weight and blood pressure of all subjects were measured and fasting blood samples were taken to measure blood glucose and lipids. The data were analyzed with T-test, &chi;2 and multiple linear regression, using SPSS11. results: Of 6391 women aged 38.8&plusmn;14.5 years participating in the study, 79% lived in the urban areas and 21% in the rural areas. The prevalence of a higher BMI was greater in urban areas in all ages. Hypertension, diabetes, total cholesterol-triglyceride and LDL-C disorders and inadequate physical activity were more prevalent in obese women than normal ones, but no significant difference was seen in HDL-C disorder and smoking between the two groups (P&lt;0.05). There was a significant positive relationship between BMI and age, blood glucose and urban residence, and a negative relationship was observed between BMI and inadequate physical activity (P&lt;0.05). Discussion: The high prevalence of obesity and the major risk factors of cardiovascular diseases in urban areas is testament to unhealthy lifestyle and insufficient physical activity of women in areas studied.Keywords . Women . Obesity . Residence . Risk factor</p
    corecore