Antibody capture radioimmunoassay for anti-rubella IgM

An M-antibody capture radioimmunoassay (MACRIA) for anti-rubella IgM was developed. Under optimum conditions positive serum specimens bound up to 20 times as much radioactivity as negative specimens. Positive reactions were expressed in arbitrary units/ml by comparison with a calibration curve derived from results obtained with dilutions of a standard serum. The specificity of the assay was confirmed by testing IgM and IgG rich fractions of positive sera. One hundred and forty specimens from blood donors, patients whose sera contained rheumatoid factor and patients with acute, non-rubella, virus infections were tested by MACRIA. No significant non-specific reactions were detected. Paired sera from acute rubella (25 patients) and individual sera from suspected rubella (69 patients) were tested for anti-rubella IgM by MACRIA and by haemagglutination inhibition following sucrose-density-gradient fractionation. There was close agreement between the two methods. The capture assay was more sensitive and could be used to detect the weak IgM response in women given RA 27/3 vaccine. After the natural infection, the MACRIA was strongly positive for two months and remained weakly so for a further two months. Repeat testing of sera demonstrated good reproducibility of the assay. MACRIA proved a simple, sensitive and specific test for anti-rubella IgM and compared favourably with currently used technique

In-service Initial Teacher Education in the Learning and Skills Sector in England: Integrating Course and Workplace Learning

The aim of the paper is to advance understanding of in-service learning and skills sector trainee teachers’ learning and propose ways of improving their learning. A conceptual framework is developed by extending Billett’s (International Journal of Educational Research 47:232–240, 2008) conceptualisation of workplace learning, as a relationally interdependent process between the opportunities workplaces afford for activities and interactions and how individuals engage with these, to a third base of participation, the affordances of the initial teacher education course. Hager and Hodkinson’s (British Educational Research Journal 35:619–638, 2009) metaphor of ‘learning as becoming’ is used to conceptualise the ways trainees reconstruct learning in a continuous transactional process of boundary crossing between course and workplace. The findings of six longitudinal case studies of trainees’ development, and evidence from other studies, illustrate the complex interrelationships between LSS workplace affordances, course affordances and trainee characteristics and the ways in which trainees reconstruct learning in each setting. The experience of teaching and interacting with learners, interactions with colleagues, and access to workplace resources and training are important workplace affordances for learning. However, some trainees have limited access to these affordances. Teaching observations, course activities and experiences as a learner are significant course affordances. Trainees’ beliefs, prior experiences and dispositions vary and significantly influence their engagement with course and workplace affordances. It is proposed that better integration of course and workplace learning through guided participation in an intentional workplace curriculum and attention to the ways trainees choose to engage with this, together with the use of practical theorising has the potential to improve trainee learning

Polynomial kernels for 3-leaf power graph modification problems

A graph G=(V,E) is a 3-leaf power iff there exists a tree T whose leaves are V and such that (u,v) is an edge iff u and v are at distance at most 3 in T. The 3-leaf power graph edge modification problems, i.e. edition (also known as the closest 3-leaf power), completion and edge-deletion, are FTP when parameterized by the size of the edge set modification. However polynomial kernel was known for none of these three problems. For each of them, we provide cubic kernels that can be computed in linear time for each of these problems. We thereby answer an open problem first mentioned by Dom, Guo, Huffner and Niedermeier (2005).Comment: Submitte

MS4a4B, a CD20 Homologue in T Cells, Inhibits T Cell Propagation by Modulation of Cell Cycle

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural killer cells (NK) and some T cell lines. But its expression in all malignant T cells, including thymoma and T hybridoma tested, was silenced. Interestingly, its expression was regulated during T cell activation. Viral vector-driven overexpression of MS4a4B in primary T cells and EL4 thymoma cells reduced cell proliferation. In contrast, knockdown of MS4a4B accelerated T cell proliferation. Cell cycle analysis showed that MS4a4B regulated T cell proliferation by inhibiting entry of the cells into S-G2/M phase. MS4a4B-mediated inhibition of cell cycle was correlated with upregulation of Cdk inhibitory proteins and decreased levels of Cdk2 activity, subsequently leading to inhibition of cell cycle progression. Our data indicate that MS4a4B negatively regulates T cell proliferation. MS4a4B, therefore, may serve as a modulator in the negative-feedback regulatory loop of activated T cell

CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes

B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction

Asymptomatic infection and family contact patterns in households of Ebola Virus Disease survivors, Sierra Leone 2015

The data set contains information on 937 people (living and dead) who were resident in the households of people who survived Ebola Virus Disease (EVD) in the Kerry Town Ebola Treatment Centre in Western Area Province, Sierra Leone, during the 2014-2016 epidemic. It includes individual and household characteristics, information on exposure levels, symptoms experienced by individuals during the period when the household was affected by EVD, outcomes, possible routes of transmission, and ELISA results from antibody testing for Ebola IgG in oral fluid. Survivor households were chosen because they were more easily contactable through the Save the Children survivors outreach programme: 123 of 152 survivors and their households were interviewed

Hepatitis E virus in blood donors in England, 2016 to 2017: from selective to universal screening

Introduction Hepatitis E virus (HEV), the most common cause of acute hepatitis in many European countries, is transmitted through consumption of processed pork but also via blood transfusion and transplantation. HEV infection can become persistent in immunocompromised individuals. Aim We aimed to determine the incidence and epidemiology of HEV infection in English blood donors since the introduction of donation screening in 2016. Methods Between March 2016 and December 2017, 1,838,747 blood donations were screened for HEV RNA. Donations containing HEV RNA were further tested for serological markers, RNA quantification and viral phylogeny. Demographics, travel and diet history were analysed for all infected donors. Results We identified 480 HEV RNA-positive blood donations during the 22-month period, most (319/480; 66%) donors were seronegative. Viral loads ranged from 1 to 3,230,000 IU/ml. All sequences belonged to genotype 3, except one which likely represents a new genotype. Most viraemic donors were over 45 years of age (279/480; 58%), donors aged between 17 and 24 years had a seven-times higher incidence of HEV infection than other donors between March and June 2016 (1:544 donations vs 1:3,830). HEV-infected blood donors were evenly distributed throughout England. Screening prevented 480 HEV RNA-positive blood donations from reaching clinical supply. Conclusion HEV screening of blood donations is a vital step in order to provide safer blood for all recipients, but especially for the immunosuppressed. The unusually high rates of HEV infection in young blood donors may provide some insight into specific risks associated with HEV infection in England

Asymptomatic infection and unrecognised Ebola virus disease in Ebola-affected households in Sierra Leone: a cross-sectional study using a new non-invasive assay for antibodies to Ebola virus.

BACKGROUND: The frequency of asymptomatic infection with Ebola virus is unclear: previous estimates vary and there is no standard test. Asymptomatic infection with Ebola virus could contribute to population immunity, reducing spread. If people with asymptomatic infection are infectious it could explain re-emergences of Ebola virus disease (EVD) without known contact. METHODS: We validated a new oral fluid anti-glycoprotein IgG capture assay among survivors from Kerry Town Ebola Treatment Centre and controls from communities unaffected by EVD in Sierra Leone. We then assessed the seroprevalence of antibodies to Ebola virus in a cross-sectional study of household contacts of the survivors. All household members were interviewed. Two reactive tests were required for a positive result, with a third test to resolve any discrepancies. FINDINGS: The assay had a specificity of 100% (95% CI 98·9-100; 339 of 339 controls tested negative) and sensitivity of 95·9% (89·8-98·9; 93 of 97 PCR-confirmed survivors tested positive). Of household contacts not diagnosed with EVD, 47·6% (229 of 481) had high level exposure (direct contact with a corpse, body fluids, or a case with diarrhoea, vomiting, or bleeding). Among the contacts, 12·0% (95% CI 6·1-20·4; 11 of 92) with symptoms at the time other household members had EVD, and 2·6% (1·2-4·7; 10 of 388) with no symptoms tested positive. Among asymptomatic contacts, seropositivity was weakly correlated with exposure level. INTERPRETATION: This new highly specific and sensitive assay showed asymptomatic infection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few transmissions. FUNDING: Wellcome Trust ERAES Programme, Save the Children

Landesque capital as an alternative to food storage in Melanesia: Irrigated taro terraces in New Georgia, Solomon Islands

In the Pacific islands, subsistence diversity made possible continuous production of food while welldeveloped exchange networks redistributed these foodstuffs as well as items within the prestige economy. All these were aspects of the ‘storage structures’ that enabled social and nutritional value to be saved, accumulated and later mobilised. In addition, there were investments in the land, landesque capital, which secured future food surpluses and so provided an alternative to food storage, in a region where the staple foods were mostly perishable, yams excepted, and food preservation was difficult. Landesque capital included such long-term improvements to productivity as terraces, mounds, irrigation channels, drainage ditches, soil structural changes and tree planting. These investments provided an effective alternative to food storage and made possible surplus production for exchange purposes. As an example, in the New Georgia group of the western Solomon Islands irrigated terraces, termed ruta, were constructed for growing the root crop taro (Colocasia esculenta). Surplus taro from ruta enabled inland groups to participate in regional exchange networks and so obtain the shell valuables that were produced by coastal groups. In this paper, we reconstruct how this exchange system worked in New Georgia using ethno-archaeological evidence, we chart its prehistoric rise and post-colonial fall, and we outline the factors that constrained its long-term expansion.Our gratitude for support during earlier fieldwork in the New Georgia group has already been expressed in previous publications. The 2014 project was supported by the Smuts Fund and Foreign Travel Fund, University of Cambridge, and by St John’s College, Cambridge.This is the accepted manuscript. The final version is available from Maney at http://dx.doi.org/10.1179/1749631414Y.000000004