Questions in/of English

Our starting point is provided by two accounts of observed lessons. The two lessons happened, at more or less the same time, in the same English department in an East London secondary school. Both lessons, observed by the second- and third-named authors, involved the shared reading of the same novel. We are interested in the difference between these two lessons, a difference that is manifested most clearly in the different ways in which questions enter in the two lessons. We argue that this difference is symptomatic of two fundamentally different versions of English as a school subject

Extracellular adenosine signaling induces CX3CL1 expression in the brain to promote experimental autoimmune encephalomyelitis

BACKGROUND: Multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) are debilitating neuroinflammatory diseases mediated by lymphocyte entry into the central nervous system (CNS). While it is not known what triggers lymphocyte entry into the CNS during neuroinflammation, blockade of lymphocyte migration has been shown to be effective in controlling neuroinflammatory diseases. Since we have previously shown that extracellular adenosine is a key mediator of lymphocyte migration into the CNS during EAE progression, we wanted to determine which factors are regulated by adenosine to modulate EAE development. METHODS: We performed a genetic analysis of wild type and CD73−/− (that are unable to produce extracellular adenosine and are protected from EAE development) to identify factors that are both important for EAE development and controlled by extracellular adenosine signaling. RESULTS: We show that extracellular adenosine triggered lymphocyte migration into the CNS by inducing the expression of the specialized chemokine/adhesion molecule CX3CL1 at the choroid plexus. In wild type mice, CX3CL1 is upregulated in the brain on Day 10 post EAE induction, which corresponds with initial CNS lymphocyte infiltration and the acute stage of EAE. Conversely, mice that cannot synthesize extracellular adenosine (CD73−/− mice) do not upregulate CX3CL1 in the brain following EAE induction and are protected from EAE development and its associated lymphocyte infiltration. Additionally, blockade of the A2A adenosine receptor following EAE induction prevents disease development and the induction of brain CX3CL1 expression. The CX3CL1 induced during EAE is found on the choroid plexus, which is the barrier between the blood and cerebral spinal fluid in the brain and is a prime entry point into the CNS for immune cells. Furthermore, CX3CL1 expression can be induced in the brains of mice and in choroid plexus cell line following A2A adenosine receptor agonist administration. Most importantly, we show that CX3CL1 blockade protects against EAE development and inhibits lymphocyte entry into the CNS. CONCLUSIONS: We conclude that extracellular adenosine is an endogenous modulator of neuroinflammation during EAE that induces CX3CL1 at the choroid plexus to trigger lymphocyte entry into the brain

CD73 Is Critical for the Resolution of Murine Colonic Inflammation

CD73 is a glycosyl-phosphatidylinositol-(GPI-) linked membrane protein that catalyzes the extracellular dephosphorylation of adenosine monophosphate (AMP) to adenosine. Adenosine is a negative regulator of inflammation and prevents excessive cellular damage. We investigated the role of extracellular adenosine in the intestinal mucosa during the development of Dextran-Sulfate-Sodium-(DSS-)salt-induced colitis in mice that lack CD73 (CD73−/−) and are unable to synthesize extracellular adenosine. We have found that, compared to wild-type (WT) mice, CD73−/− mice are highly susceptible to DSS-induced colitis. CD73−/− mice exhibit pronounced weight loss, slower weight recovery, an increase in gut permeability, a decrease in expression of tight junctional adhesion molecules, as well as unresolved inflammation following the removal of DSS. Moreover, colonic epithelia in CD73−/− mice exhibited increased TLR9 expression, high levels of IL-1β and TNF-α, and constitutive activation of NF-κB. We conclude that CD73 expression in the colon is critical for regulating the magnitude and the resolution of colonic immune responses.National Institutes of Health (U.S.) (grant A1072434-A2)National Institutes of Health (U.S.) (grant R01NS063011

Прочностные характеристики армированного песчаного грунта

Laboratory tests on determination of reinforced sandy soil strength characteristics (angle of internal friction, specific cohesive force) have been carried out with the help of a specially designed instrument and proposed methodology. Analysis of the obtained results has revealed that cohesive forces are brought about in reinforced sandy soil and an angle of internal soil friction becomes larger in comparison with non-reinforced soil.Проведены лабораторные испытания по определению прочностных характеристик (угла внутреннего трения, удельной силы сцепления) армированного песчаного грунта с помощью специально сконструированного прибора и предлагаемой методики. Анализ полученных результатов показывает, что в армированном песчаном грунте возникают силы связности, а угол внутреннего трения грунта становится значительно большим по сравнению с неармированным

Student performance assessment using clustering techniques

The application of informatics in the university system management allows managers to count with a great amount of data which, rationally treated, can offer significant help for the student programming monitoring. This research proposes the use of clustering techniques as a useful tool of management strategy to evaluate the progression of the students’ behavior by dividing the population into homogeneous groups according to their characteristics and skills. These applications can help both the teacher and the student to improve the quality of education. The selected method is the data grouping analysis by means of fuzzy logic using the Fuzzy C-means algorithm to achieve a standard indicator called Grade, through an expert system to enable segmentation.Universidad de la Costa, 2 Universidad Nacional Experimental Politécnica “Antonio José de Sucre”, Universidad Simón Bolívar, Corporación Universitaria Latinoamericana, Corporación Universitaria Minuto de Dios

Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells

A hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we used live cell imaging to track Mtb infection outcomes in individual primary human macrophages. Internalization of Mtb aggregates caused macrophage death, and phagocytosis of large aggregates was more cytotoxic than multiple small aggregates containing similar numbers of bacilli. Macrophage death did not result in clearance of Mtb. Rather, it led to accelerated intracellular Mtb growth regardless of prior activation or macrophage type. In contrast, bacillary replication was controlled in live phagocytes. Mtb grew as a clump in dead cells, and macrophages which internalized dead infected cells were very likely to die themselves, leading to a cell death cascade. This demonstrates how pathogen virulence can be achieved through numbers and aggregation states. DOI: http://dx.doi.org/10.7554/eLife.22028.00

A qualitative study of women's experiences of communication in antenatal care: Identifying areas for action

To identify key features of communication across antenatal (prenatal) care that are evaluated positively or negatively by service users. Focus groups and semi-structured interviews were used to explore communication experiences of thirty pregnant women from diverse social and ethnic backgrounds affiliated to a large London hospital. Data were analysed using thematic analysis. Women reported a wide diversity of experiences. From the users’ perspective, constructive communication on the part of health care providers was characterised by an empathic conversational style, openness to questions, allowing sufficient time to talk through any concerns, and pro-active contact by providers (e.g. text message appointment reminders). These features created reassurance, facilitated information exchange, improved appointment attendance and fostered tolerance in stressful situations. Salient features of poor communication were a lack of information provision, especially about the overal

Single-cell RNA sequencing of liver fine-needle aspirates captures immune diversity in the blood and liver in chronic hepatitis B patients

Background and Aims: HBV infection is restricted to the liver, where it drives exhaustion of virus-specific T and B cells and pathogenesis through dysregulation of intrahepatic immunity. Our understanding of liver-specific events related to viral control and liver damage has relied almost solely on animal models, and we lack useable peripheral biomarkers to quantify intrahepatic immune activation beyond cytokine measurement. Our objective was to overcome the practical obstacles of liver sampling using fine-needle aspiration and develop an optimized workflow to comprehensively compare the blood and liver compartments within patients with chronic hepatitis B using single-cell RNA sequencing. Approach and Results: We developed a workflow that enabled multi-site international studies and centralized single-cell RNA sequencing. Blood and liver fine-needle aspirations were collected, and cellular and molecular captures were compared between the Seq-Well S3 picowell-based and the 10× Chromium reverse-emulsion droplet–based single-cell RNA sequencing technologies. Both technologies captured the cellular diversity of the liver, but Seq-Well S3 effectively captured neutrophils, which were absent in the 10× dataset. CD8 T cells and neutrophils displayed distinct transcriptional profiles between blood and liver. In addition, liver fine-needle aspirations captured a heterogeneous liver macrophage population. Comparison between untreated patients with chronic hepatitis B and patients treated with nucleoside analogs showed that myeloid cells were highly sensitive to environmental changes while lymphocytes displayed minimal differences. Conclusions: The ability to electively sample and intensively profile the immune landscape of the liver, and generate high-resolution data, will enable multi-site clinical studies to identify biomarkers for intrahepatic immune activity in HBV and beyond.</p

Expression and Function of Serotonin 2A and 2B Receptors in the Mammalian Respiratory Network

Neurons of the respiratory network in the lower brainstem express a variety of serotonin receptors (5-HTRs) that act primarily through adenylyl cyclase. However, there is one receptor family including 5-HT2A, 5-HT2B, and 5-HT2C receptors that are directed towards protein kinase C (PKC). In contrast to 5-HT2ARs, expression and function of 5-HT2BRs within the respiratory network are still unclear. 5-HT2BR utilizes a Gq-mediated signaling cascade involving calcium and leading to activation of phospholipase C and IP3/DAG pathways. Based on previous studies, this signal pathway appears to mediate excitatory actions on respiration. In the present study, we analyzed receptor expression in pontine and medullary regions of the respiratory network both at the transcriptional and translational level using quantitative RT-PCR and self-made as well as commercially available antibodies, respectively. In addition we measured effects of selective agonists and antagonists for 5-HT2ARs and 5-HT2BRs given intra-arterially on phrenic nerve discharges in juvenile rats using the perfused brainstem preparation. The drugs caused significant changes in discharge activity. Co-administration of both agonists revealed a dominance of the 5-HT2BR. Given the nature of the signaling pathways, we investigated whether intracellular calcium may explain effects observed in the respiratory network. Taken together, the results of this study suggest a significant role of both receptors in respiratory network modulation