355 research outputs found
RUNX1 regulates a transcription program that affects the dynamics of cell cycle entry of naive resting B cells
RUNX1 is a transcription factor that plays key roles in hematopoietic development and in hematopoiesis and lymphopoiesis. In this article, we report that RUNX1 regulates a gene expression program in naive mouse B cells that affects the dynamics of cell cycle entry in response to stimulation of the BCR. Conditional knockout of Runx1 in mouse resting B cells resulted in accelerated entry into S-phase after BCR engagement. Our results indicate that Runx1 regulates the cyclin D2 (Ccnd2) gene, the immediate early genes Fosl2, Atf3, and Egr2, and the Notch pathway gene Rbpj in mouse B cells, reducing the rate at which transcription of these genes increases after BCR stimulation. RUNX1 interacts with the chromatin remodeler SNF-2-related CREB-binding protein activator protein (SRCAP), recruiting it to promoter and enhancer regions of the Ccnd2 gene. BCR-mediated activation triggers switching between binding of RUNX1 and its paralog RUNX3 and between SRCAP and the switch/SNF remodeling complex member BRG1. Binding of BRG1 is increased at the Ccnd2 and Rbpj promoters in the Runx1 knockout cells after BCR stimulation. We also find that RUNX1 exerts positive or negative effects on a number of genes that affect the activation response of mouse resting B cells. These include Cd22 and Bank1, which act as negative regulators of the BCR, and the IFN receptor subunit gene Ifnar1 The hyperresponsiveness of the Runx1 knockout B cells to BCR stimulation and its role in regulating genes that are associated with immune regulation suggest that RUNX1 could be involved in regulating B cell tolerance
The effect of nitric oxide on the pressure of the acutely obstructed ureter
Acute ureteral obstruction leads to changes in pressure inside the ureter, interrupting ureter function. The aim of our study is to explore the relationship between nitric oxide (NO) concentration and pressure in the ureter and to observe the effects of nitric oxide on the revival of renal function. We created the animal models by embedding balloons in the lower ureters of anesthetized dogs and expanding them to simulate acute ureteral obstruction. First, the test animals were pre-treated intravenously with different doses of L-NAME (non-selective nitric oxide synthase inhibitor) to inhibit nitric oxide synthase (NOS), and 10 min later, each subject was administered an intravenous dose of isoproterenol (10 μg/kg). We measured ureter pressure (UP), total and peak concentrations of NO (using an NO monitor, model inNO-T) in ureteral urine, and the volume of the urine (UFV) leaking from the balloon edge. After a certain amount of time had elapsed, it became clear that the dose of L-NAME was inversely related to the total and peak concentrations of NO, the rate of change in UP, and the volume of urine produced. We conclude that L-NAME prevents the NOS from inhibiting the release of NO, then inhibits the effect of isoproterenol reducing the pressure of the acute obstructive ureter. Inversely, we think that NO can reduce the pressure of the acute obstructive ureter and make the obstructive ureter recanalization. And when more the concentration of nitric oxide, the more the pressure will be reduced, and more urine will be collected
Acupressure for smoking cessation – a pilot study
BACKGROUND: Tobacco smoking is a serious risk to health: several therapies are available to assist those who wish to stop. Smokers who approach publicly funded stop-smoking clinics in the UK are currently offered nicotine replacement therapy (NRT) or bupropion, and group behaviour therapy, for which there is evidence of effectiveness. Acupuncture and acupressure are also used to help smokers, though a systematic review of the evidence of their effectiveness was inconclusive. The aim of this pilot project was to determine the feasibility of a study to test acupressure as an adjunct to one anti-smoking treatment currently offered, and to inform the design of the study. METHODS: An open randomised controlled pilot study was conducted within the six week group programme offered by the Smoking Advice Service in Plymouth, UK. All participants received the usual treatment with NRT and group behavioural therapy, and were randomised into three groups: group A with two auricular acupressure beads, group B with one bead, and group C with no additional therapy. Participants were taught to press the beads when they experienced cravings. Beads were worn in one ear for four weeks, being replaced as necessary. The main outcome measures assessed in the pilot were success at quitting (expired CO ≤ 9 ppm), the dose of NRT used, and the rating of withdrawal symptoms using the Mood and Symptoms Scale. RESULTS: From 49 smokers attending four clinics, 24 volunteered to participate, 19 attended at least once after quitting, and seven remained to the final week. Participants who dropped out reported significantly fewer previous quit attempts, but no other significant differences. Participants reported stimulating the beads as expected during the initial days after quitting, but most soon reduced the frequency of stimulation. The discomfort caused by the beads was minor, and there were no significant side effects. There were technical problems with adhesiveness of the dressing. Reporting of NRT consumption was poor, with much missing data, but reporting of ratings of withdrawal symptom scores was nearly complete. However, these showed no significant changes or differences between groups for any week. CONCLUSION: Any effects of acupressure on smoking withdrawal, as an adjunct to the use of NRT and behavioural intervention, are unlikely to be detectable by the methods used here and further preliminary studies are required before the hypothesis can be tested
Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis
Peer reviewedPublisher PD
Carotid Artery Wall Imaging: Perspective and Guidelines from the ASNR Vessel Wall Imaging Study Group and Expert Consensus Recommendations of the American Society of Neuroradiology
SUMMARY: Identification of carotid artery atherosclerosis is conventionally based on measurements of luminal stenosis and surface irregularities using in vivo imaging techniques including sonography, CT and MR angiography, and digital subtraction angiography. However, histopathologic studies demonstrate considerable differences between plaques with identical degrees of stenosis and indicate that certain plaque features are associated with increased risk for ischemic events. The ability to look beyond the lumen using highly developed vessel wall imaging methods to identify plaque vulnerable to disruption has prompted an active debate as to whether a paradigm shift is needed to move away from relying on measurements of luminal stenosis for gauging the risk of ischemic injury. Further evaluation in randomized clinical trials will help to better define the exact role of plaque imaging in clinical decision-making. However, current carotid vessel wall imaging techniques can be informative. The goal of this article is to present the perspective of the ASNR Vessel Wall Imaging Study Group as it relates to the current status of arterial wall imaging in carotid artery disease
Concordance of sibling's recall of measures of childhood socioeconomic position
<p>Abstract</p> <p>Background</p> <p>Studies of socioeconomic determinants of health often rely on recalled information on childhood socioeconomic position, despite limited evidence of the validity of this information. This study examined concordance between siblings of recalled measures of childhood socioeconomic position.</p> <p>Methods</p> <p>This cross-sectional study examined reports by 1280 adult sibling pairs in the National Survey of Midlife Development in the United States of seven measures of childhood socioeconomic position: father's occupation (in 9 categories), father having a professional occupation, father being a supervisor at work, father's education level, mother's education level, receipt of welfare payments, and subjective appraisal of being better or worse off financially than others.</p> <p>Results</p> <p>Concordance was high for father's professional occupation (0.97; 95% confidence interval (CI) 0.96, 0.98), father's occupation in 9 categories (0.76; 95% CI 0.73, 0.80), and receipt of welfare payments (0.95; 95% CI 0.93, 0.97). Concordance was lower for father's and mother's education level, and lowest for subjective appraisal of socioeconomic position (0.60; 95% CI 0.57, 0.64). Concordance of parental education was lower for sibling pairs with high school educations or less.</p> <p>Conclusion</p> <p>Concordance of recalled measures of childhood socioeconomic position by siblings is generally but not uniformly high.</p
MRI of the lung (2/3). Why … when … how?
Background
Among the modalities for lung imaging, proton magnetic resonance imaging (MRI) has been the latest to be introduced into clinical practice. Its value to replace X-ray and computed tomography (CT) when radiation exposure or iodinated contrast material is contra-indicated is well acknowledged: i.e. for paediatric patients and pregnant women or for scientific use. One of the reasons why MRI of the lung is still rarely used, except in a few centres, is the lack of consistent protocols customised to clinical needs.
Methods
This article makes non-vendor-specific protocol suggestions for general use with state-of-the-art MRI scanners, based on the available literature and a consensus discussion within a panel of experts experienced in lung MRI.
Results
Various sequences have been successfully tested within scientific or clinical environments. MRI of the lung with appropriate combinations of these sequences comprises morphological and functional imaging aspects in a single examination. It serves in difficult clinical problems encountered in daily routine, such as assessment of the mediastinum and chest wall, and even might challenge molecular imaging techniques in the near future.
Conclusion
This article helps new users to implement appropriate protocols on their own MRI platforms.
Main Messages
• MRI of the lung can be readily performed on state-of-the-art 1.5-T MRI scanners.
• Protocol suggestions based on the available literature facilitate its use for routine
• MRI offers solutions for complicated thoracic masses with atelectasis and chest wall invasion.
• MRI is an option for paediatrics and science when CT is contra-indicate
Considerations about quality in model-driven engineering
The final publication is available at Springer via http://dx.doi.org/10.1007/s11219-016-9350-6The virtue of quality is not itself a subject; it depends on a subject. In the software engineering field, quality means good software products that meet customer expectations, constraints, and requirements. Despite the numerous approaches, methods, descriptive models, and tools, that have been developed, a level of consensus has been reached by software practitioners. However, in the model-driven engineering (MDE) field, which has emerged from software engineering paradigms, quality continues to be a great challenge since the subject is not fully defined. The use of models alone is not enough to manage all of the quality issues at the modeling language level. In this work, we present the current state and some relevant considerations regarding quality in MDE, by identifying current categories in quality conception and by highlighting quality issues in real applications of the model-driven initiatives. We identified 16 categories in the definition of quality in MDE. From this identification, by applying an adaptive sampling approach, we discovered the five most influential authors for the works that propose definitions of quality. These include (in order): the OMG standards (e.g., MDA, UML, MOF, OCL, SysML), the ISO standards for software quality models (e.g., 9126 and 25,000), Krogstie, Lindland, and Moody. We also discovered families of works about quality, i.e., works that belong to the same author or topic. Seventy-three works were found with evidence of the mismatch between the academic/research field of quality evaluation of modeling languages and actual MDE practice in industry. We demonstrate that this field does not currently solve quality issues reported in industrial scenarios. The evidence of the mismatch was grouped in eight categories, four for academic/research evidence and four for industrial reports. These categories were detected based on the scope proposed in each one of the academic/research works and from the questions and issues raised by real practitioners. We then proposed a scenario to illustrate quality issues in a real information system project in which multiple modeling languages were used. For the evaluation of the quality of this MDE scenario, we chose one of the most cited and influential quality frameworks; it was detected from the information obtained in the identification of the categories about quality definition for MDE. We demonstrated that the selected framework falls short in addressing the quality issues. Finally, based on the findings, we derive eight challenges for quality evaluation in MDE projects that current quality initiatives do not address sufficiently.F.G, would like to thank COLCIENCIAS (Colombia) for funding this work through the Colciencias Grant call 512-2010. This work has been supported by the Gene-ralitat Valenciana Project IDEO (PROMETEOII/2014/039), the European Commission FP7 Project CaaS (611351), and ERDF structural funds.Giraldo-Velásquez, FD.; España Cubillo, S.; Pastor López, O.; Giraldo, WJ. (2016). Considerations about quality in model-driven engineering. Software Quality Journal. 1-66. https://doi.org/10.1007/s11219-016-9350-6S166(1985). Iso information processing—documentation symbols and conventions for data, program and system flowcharts, program network charts and system resources charts. ISO 5807:1985(E) (pp. 1–25).(2011). Iso/iec/ieee systems and software engineering – architecture description. 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Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice
<p>Abstract</p> <p>Background</p> <p>Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level.</p> <p>Methods</p> <p>Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done.</p> <p>Results</p> <p>Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as <it>CCL3</it>, <it>CCL4</it>, <it>CXCL2</it>, and <it>MMP12 </it>in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as <it>S100A8</it>, <it>S100A9 </it>and <it>MMP9</it>.</p> <p>Conclusions</p> <p>Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.</p
Why Amphibians Are More Sensitive than Mammals to Xenobiotics
Dramatic declines in amphibian populations have been described all over the world since the 1980s. The evidence that the sensitivity to environmental threats is greater in amphibians than in mammals has been generally linked to the observation that amphibians are characterized by a rather permeable skin. Nevertheless, a numerical comparison of data of percutaneous (through the skin) passage between amphibians and mammals is lacking. Therefore, in this investigation we have measured the percutaneous passage of two test molecules (mannitol and antipyrine) and three heavily used herbicides (atrazine, paraquat and glyphosate) in the skin of the frog Rana esculenta (amphibians) and of the pig ear (mammals), by using the same experimental protocol and a simple apparatus which minimizes the edge effect, occurring when the tissue is clamped in the usually used experimental device
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