Fv antibodies to aflatoxin B1 derived from a pre-immunized antibody phage display library system

The production and characterization of recombinant antibodies to aflatoxin B[SUB1] (AFB[SUB1]), a potent mycotoxin and carcinogen is described. The antibody fragments produced were then applied for use in a surface plasmon resonance-based biosensor (BIAcore), which measures biomolecular interactions in 'real-time'. Single chain Fv (scFv) antibodies were generated to aflatoxin B1 from an established phage display system, which incorporated a range of different plasmids for efficient scFv expression. The scFv's were used in the development of a competitive ELISA, and also for the development of surface plasmon resonance (SPR)-based inhibition immunoassays. They were found to be suitable for the detection of AFB[SUB1], in this format, with the assays being sensitive and reproducible

The major element of 1-year prognosis in acute coronary syndromes is severity of initial clinical presentation: Results from the French MONICA registries

SummaryBackgroundWhile the death rate from acute coronary syndromes (ACS) has been in decline for more than 50years, out-of-hospital mortality remains high despite improvements in care.AimTo evaluate the importance of out-of-hospital mortality and identify the main predictors of in-hospital and 1-year mortality in France.MethodsAnalyses were based on data from the French MONICA population-based registry, which included all cases of ACS occurring in people aged 35–74years during 2006 in three geographic areas in France. We first evaluated out-of-hospital mortality; then, using data from patients with incident ACS who reached hospital alive, Cox models were performed to determine the main predictors of 1-year mortality. The number of attributable deaths was assessed for variables of interest.ResultsAfter 1-year follow-up, case-fatality was 29.3% for incident events (n=2547); the proportion of out-of-hospital deaths was 70.3%, and 91.5% of deaths occurred in the 28days following the ACS. On multivariable analysis, the number of attributable deaths associated with three scenarios (out-of-hospital life-and-death emergency, hospitalization before ACS occurrence, and lack of coronary angiography) was 130 (accounting for 59% of deaths occurring after reaching the hospital) during 1-year follow-up. These scenarios corresponded to patients with an initial severe clinical presentation in whom rates of use of specific treatments and invasive procedures were very low.ConclusionA large proportion of fatalities after an ACS occurs in the out-of-hospital phase. Moreover, the major component of 1-year mortality is associated with a poor prognosis at initial presentation. This finding highlights the importance of cardiovascular prevention, population education and better out-of-hospital emergency management in improving prognosis after an ACS

Editorial

The nine articles in the special issue highlight two main issues related to the pandemic- induced experimentation in teaching and learning: As indicated by the diversity of the authors’ physical locations, COVID and emergency-remote teaching affected HEIs at a nearly global scale. Authors in this issue come from European countries (Switzerland, Germany), North America (the USA) as well as the southern hemisphere (South Africa). Given the breadth of COVID-related (change) experiences, the insights presented in this issue can be relevant to many HEIs across the globe, notwithstanding their cultural and institutional specificities. In addition, and of high relevance to us, the articles collected here focus both on different positions or roles (students, faculty, management) as well as on different levels of teaching and learning in higher education (teaching and learning, curricular or institutional levels). While most contributions focus on the student experience during COVID, others investigate faculty/instructors’ perspectives including faculty development. Yet another group takes a more systemic, institutional point of view. It could be argued that higher-education research takes up a multi-level perspective when exploring change and the new normal

MUG-Mel2, a novel highly pigmented and well characterized NRAS mutated human melanoma cell line

NRAS mutation in melanoma has been associated with aggressive tumor biology and poor prognosis. Although targeted therapy has been tested for NRAS mutated melanoma, response rates still appear much weaker, than in BRAF mutated melanoma. While plenty of cell lines exist, however, only few melanogenic cell lines retain their in vivo characteristics. In this work we present an intensively pigmented and well-characterized cell line derived from a highly aggressive NRAS mutated cutaneous melanoma, named MUG-Mel2. We present the clinical course, unique morphology, angiogenic properties, growth characteristics using in vivo experiments and 3D cell culture, and results of the exome gene sequencing of an intensively pigmented melanogenic cell line MUG-Mel2, derived from a cutaneous metastasis of an aggressive NRAS p. Q61R mutated melanoma. Amongst several genetic alterations, mutations in GRIN2A, CREBP, PIK3C2G, ATM, and ATR were present. These mutations, known to reinforce DNA repair problems in melanoma, might serve as potential treatment targets. The aggressive and fast growing behavior in animal models and the obtained phenotype in 3D culture reveal a perfect model for research in the field of NRAS mutated melanoma.Peer reviewe

A new role for complement C3: regulation of antigen processing through an inhibitory activity.

International audienceIncreasing evidence underlines the involvement of complement component C3 in the establishment of acquired immunity which appears to play a complex role and to act at different levels. As antigen proteolysis by antigen presenting cells is a key event in the control of antigen presentation efficiency, and consequently in the quality of the immune response, we investigated whether C3 could modulate this step. Our results demonstrate for the first time that C3 can interfere with antigen proteolysis: (i) proteolysis of tetanus toxin (TT) by the lysosomal fraction from a human monocytic cell line (U937) is impaired in the presence of C3, (ii) this effect is C3-specific and involves the C3c fragment of the protein, (iii) C3c is effective even after disulfide disruption, but none of its three constitutive peptides is individually accountable for this inhibitory effect and (iv) the target-protease(s) exhibit(s) a serine-protease activity. The physiological relevance of our results is demonstrated by experiments showing a subcellular colocalisation of TT and C3 after their uptake by U937 and the reduction of TT proteolysis once internalised together with C3. These results highlight a novel role for C3 that broadens its capacity to modulate acquired immune response

A Novel Cre Recombinase Imaging System for Tracking Lymphotropic Virus Infection In Vivo

BACKGROUND:Detection, isolation, and identification of individual virus infected cells during long term infection are critical to advance our understanding of mechanisms of pathogenesis for latent/persistent viruses. However, current approaches to study these viruses in vivo have been hampered by low sensitivity and effects of cell-type on expression of viral encoded reporter genes. We have designed a novel Cre recombinase (Cre)-based murine system to overcome these problems, and thereby enable tracking and isolation of individual in vivo infected cells. METHODOLOGY/PRINCIPAL FINDINGS:Murine gammaherpesvirus 68 (MHV-68) was used as a prototypic persistent model virus. A Cre expressing recombinant virus was constructed and characterised. The virus is attenuated both in lytic virus replication, producing ten-fold lower lung virus titres than wild type virus, and in the establishment of latency. However, despite this limitation, when the sEGFP7 mouse line containing a Cre-activated enhanced green fluorescent protein (EGFP) was infected with the Cre expressing virus, sites of latent and persistent virus infection could be identified within B cells and macrophages of the lymphoid system on the basis of EGFP expression. Importantly, the use of the sEGFP7 mouse line which expresses high levels of EGFP allowed individual virus positive cells to be purified by FACSorting. Virus gene expression could be detected in these cells. Low numbers of EGFP positive cells could also be detected in the bone marrow. CONCLUSIONS/SIGNIFICANCE:The use of this novel Cre-based virus/mouse system allowed identification of individual latently infected cells in vivo and may be useful for the study and long-term monitoring of other latent/persistent virus infections

A Centennial Retrospective on Charles Williams

Edited transcript of a panel discussion (including audience contributions) at the 17th Mythopoeic Society Conference

Integrating Data Science and Earth Science

This open access book presents the results of three years collaboration between earth scientists and data scientists, in developing and applying data science methods for scientific discovery. The book will be highly beneficial for other researchers at senior and graduate level, interested in applying visual data exploration, computational approaches and scientifc workflows

Effect of a web-based chronic disease management system on asthma control and health-related quality of life: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Asthma is a prevalent and costly disease resulting in reduced quality of life for a large proportion of individuals. Effective patient self-management is critical for improving health outcomes. However, key aspects of self-management such as self-monitoring of behaviours and symptoms, coupled with regular feedback from the health care team, are rarely addressed or integrated into ongoing care. Health information technology (HIT) provides unique opportunities to facilitate this by providing a means for two way communication and exchange of information between the patient and care team, and access to their health information, presented in personalized ways that can alert them when there is a need for action. The objective of this study is to evaluate the acceptability and efficacy of using a web-based self-management system, My Asthma Portal (MAP), linked to a case-management system on asthma control, and asthma health-related quality of life.</p> <p>Methods</p> <p>The trial is a parallel multi-centered 2-arm pilot randomized controlled trial. Participants are randomly assigned to one of two conditions: a) MAP and usual care; or b) usual care alone. Individuals will be included if they are between 18 and 70, have a confirmed asthma diagnosis, and their asthma is classified as not well controlled by their physician. Asthma control will be evaluated by calculating the amount of fast acting beta agonists recorded as dispensed in the provincial drug database, and asthma quality of life using the Mini Asthma Related Quality of Life Questionnaire. Power calculations indicated a needed total sample size of 80 subjects. Data are collected at baseline, 3, 6, and 9 months post randomization. Recruitment started in March 2010 and the inclusion of patients in the trial in June 2010.</p> <p>Discussion</p> <p>Self-management support from the care team is critical for improving chronic disease outcomes. Given the high volume of patients and time constraints during clinical visits, primary care physicians have limited time to teach and reinforce use of proven self-management strategies. HIT has the potential to provide clinicians and a large number of patients with tools to support health behaviour change.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN34326236">ISRCTN34326236</a>.</p

Metaphors in Nanomedicine: The Case of Targeted Drug Delivery

International audienceThe promises of nanotechnology have been framed by a variety of metaphors, that not only channel the attention of the public, orient the questions asked by researchers, and convey epistemic choices closely linked to ethical preferences. In particular, the image of the 'therapeutic missile' commonly used to present targeted drug delivery devices emphasizes precision, control, surveillance and efficiency. Such values are highly praised in the current context of crisis of pharmaceutical innovation where military metaphors foster a general mobilization of resources from multiple fields of cutting-edge research. The missile metaphor, reminiscent of Paul Ehrlich's 'magic bullet', has framed the problem in simple terms: how to deliver the right dose in the right place at the right moment? Chemists, physicists and engineers who design multi-functional devices operating in vitro can think in such terms, as long as the devices are not actually operating through the messy environment of the body. A close look at what has been done and what remains to be done suggests that the metaphor of the "therapeutic missile" is neither sufficient, nor even necessary. Recent developments in nanomedicine suggest that therapeutic efficacy cannot be obtained without negotiating with the biological milieu and taking advantage of what it affords. An 'oïkological' approach seems more appropriate, more heuristic and more promising than the popular missile. It is based on the view of organism as an oikos that has to be carefully managed. The dispositions of nanocapsules have to be coupled with the affordances of the environment. As it requires dealing with nanoparticles as relational entities (defined by their potential for interactions) rather than as stable substances (defined by intrinsic properties) this metaphor eventually might well change research priorities in nanotechnology in general