Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion

This is the final version. Available from the publisher via the DOI in this record.To colonise their host, pathogens must counter local environmental and immunological challenges. Here, we reveal that the fungal pathogen Candida albicans exploits diverse host-associated signals to promote immune evasion by masking of a major pathogen-associated molecular pattern (PAMP), β-glucan. Certain nutrients, stresses and antifungal drugs trigger β-glucan masking, whereas other inputs, such as nitrogen sources and quorum sensing molecules, exert limited effects on this PAMP. In particular, iron limitation triggers substantial changes in the cell wall that reduce β-glucan exposure. This correlates with reduced phagocytosis by macrophages and attenuated cytokine responses by peripheral blood mononuclear cells. Iron limitation-induced β-glucan masking depends on parallel signalling via the iron transceptor Ftr1 and the iron-responsive transcription factor Sef1, and the protein kinase A pathway. Our data reveal that C. albicans exploits a diverse range of specific host signals to trigger protective anticipatory responses against impending phagocytic attack and promote host colonisation.Medical Research Council (MRC)European CommissionWellcome Trus

Microscopic examination of bone marrow aspirates in malignant disorders of haematopoiesis—a comparison of two slide preparation techniques

It is mandatory to perform microscopic examinations of bone marrow aspirates during the diagnosis of many neoplastic haematopoiesis disorders. In 2008, The International Committee for Standardization in Hematology recommended the use of two types of slides for the microscopic evaluation of bone marrow: wedge-spread film and crush film slides. Because these techniques have not yet been compared, we performed such a comparison. Routine bone marrow samples from 250 patients diagnosed due to different neoplastic haematological disorders were evaluated. The major differences between the two compared techniques were identified in 13 patients with non-Hodgkin’s lymphoma, seven patients with systemic mastocytosis and 11 patients with acute leukaemias or myelodysplastic syndromes or chronic myelomonocytic leukaemia. Differences were noted also in many patients with multiple myeloma, but the clinical significance of these discrepancies was rather modest. The major causes of the differences observed seemed to be the dilution of marrow with blood cells and the focal growth of many neoplastic cells. We believe that the crush technique is more advantageous compared to the wedge-spread films. Therefore, we recommend the use of crush films as the primary method for establishing a diagnosis or for making therapeutic decisions based on the microscopic examination of bone marrow

The History You Don’t Know, and the History You Do: The Promise of Signature Pedagogies in History Education

The persistent separation of subject-matter content and pedagogical training in traditional teacher education programs has made it difficult for many beginning teachers to establish a base of knowledge they can use to develop pedagogical content knowledge as their careers unfold. While existing efforts to bridge this gap have focused on intensive collaborations between education faculty and their colleagues in disciplinary fields, or on the integration of disciplinary knowledge into teacher education coursework, work still can be done to address the problem of providing beginning teachers with the balance of deep and flexible content knowledge complemented by practical teaching maneuvers that so many of them crave. This chapter explores the possibility of addressing this gap via the development of signature pedagogies, following the lead established in many other professional fields, paying special attention to Lee Shulman’s conceptualization of the idea and its potential impact on teacher education in history

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

The Use of the S-Quattro Dynamic External Fixator for the Treatment of Intra-Articular Phalangeal Fractures: A Review of the Literature

Intra-articular phalangeal fractures are a common injury. If left untreated, these injuries can lead to poor functional outcome with severe dehabilitating consequences, especially in younger patients

Comparison of haematological parameters determined by the Sysmex KX - 2IN automated haematology analyzer and the manual counts

<p>Abstract</p> <p>Background</p> <p>This study was designed to determine the correlation between heamatological parameters by Sysmex KX-21N automated hematology analyzer with the manual methods.</p> <p>Method</p> <p>Sixty (60) subjects were randomly selected from both apparently healthy subjects and those who have different blood disorders from the University of Teaching Hospital (UNTH), Ituku-Ozalla, Enugu, Enugu State, Nigeria. Three (3)mls of venous blood sample was collected aseptically from each subject into tri-potassium ethylenediamine tetra-acetic acid (K₃EDTA) for the analysis of haematological parameters using the automated and the manual methods.</p> <p>Results</p> <p>The blood film report by the manual method showed that 50% of the subjects were normocytic-normochromic while the other 50% revealed different abnormal blood pictures. Also, there were statistically significant differences (p < 0.05) in mean cell hemoglobin concentrations (MCHC) between the two methods. Similarly, the mean (S.E) values of hemoglobin, packed cell volume, platelet and total white cell counts demonstrated statistically significant difference (p < 0.001) and correlated positively when both methods were compared.</p> <p>Conclusion</p> <p>From the present study, it can be concluded that the automated hematology analyzer readings correlated well with readings by the standard manual method, although the latter method gave additional diagnostic information on the blood pictures. While patients' care and laboratory operations could be optimized by using manual microscopic examination as a reflective substitute for automated methods, usage of automated method would ease our workload and save time for patients.</p

Dense pedestrian crowds versus granular packings: An analogy of sorts

Analogies between the dynamics of pedestrian crowds and granular media have long been hinted at.They seem all the more promising as the crowd is (very) dense, in which case the mechanical constraints prohibiting overlapsmight prevail over the decisional component of pedestrian dynamics. These analogies and their origins are probed in two distinct settings, (i) a flow through a narrow bottleneck and (ii) crossing of a static assembly by an intruder. Several quantitative similarities have been reported for the former setting and are discussed here, while setting (ii) reveals discrepancies in the response pattern, which areascribed to the pedestrians' ability to perceive, anticipate and self-propel