The societal roles and responsibilities of plant scientists in the context of genome-edited crops

Societal Impact Statement The societal debate on the use of genome-edited crops has been polarised from the start. While policymakers struggle to democratically resolve this dilemma, plant scientists have been criticised for taking up advocative roles and thereby risking further polarisation. This study demonstrates how plant scientists themselves perceive their roles and responsibilities. Indeed, those scientists active in the debate were found to fulfil advocative roles, and there seems to be an underlying, persistent?and very traditional?view on roles and responsibilities of scientists within the community. Critical reflection on this view is required for better democratic dialogue and decision-making. More interdisciplinary interaction could facilitate this reflection. Summary In this paper, we examine how plant scientists from Wageningen University and Research (WUR) demarcate their roles and responsibilities in relation to the societal impact of their research, in response to calls for public legitimacy of their research, and within the societal debate on the governance of genome-edited crops (GE crops) in Europe. We analysed 16 semi-structured interviews, 5-day journals, and (social) media contributions of plant scientists at WUR. Our study demonstrates that the perceived roles and responsibilities of the interviewees were aligned with the ideal of the scientist as value-free, as separate from society, and as producing knowledge that leads to unproblematic societal benefits through industry. When confronted with the polarised debate on the governance of genome editing (GE) technology, the reflexivity that our respondents had demonstrated in general, tended to be dispersed. Respondents rarely considered the GE crop debate, or their own position, to be value-based. Those respondents active in the debate were found to fulfil advocative roles, and they struggled to recognise the validity of viewpoints other than their own. We hypothesise that this decreased reflexive capacity is a product of the long-term polarisation of the GM/GE debate, mediated by both their conceptual alignment with the linear model of innovation and their limited interactions outside of their field. In order to better align the perspectives of social and natural scientists on the topic of science-responsibility, and to constructively contribute to the debate on GE crops, we argue for more interaction between the these two communities

Novel Nuclear Partnering Role of EPS8 With FOXM1 in Regulating Cell Proliferation

One hallmark of cancer cells is sustaining proliferative signaling that leads to uncontrolled cell proliferation. Both the Forkhead box (FOX) M1 transcription factor and the Epidermal Growth Factor (EGF) receptor Pathway Substrate 8 (EPS8) are known to be activated by mitogenic signaling and their levels upregulated in cancer. Well-known to regulate Rac-mediated actin remodeling at the cell cortex, EPS8 carries a nuclear localization signal but its possible nuclear role remains unclear. Here, we demonstrated interaction of FOXM1 with EPS8 in yeast two-hybrid and immunoprecipitation assays. Immunostaining revealed co-localization of the two proteins during G2/M phase of the cell cycle. EPS8 became nuclear localized when CRM1/Exportin 1-dependent nuclear export was inhibited by Leptomycin B, and a functional nuclear export signal could be identified within EPS8 using EGFP-tagging and site-directed mutagenesis. Downregulation of EPS8 using shRNAs suppressed expression of FOXM1 and the FOXM1-target CCNB1, and slowed down G2/M transition in cervical cancer cells. Chromatin immunoprecipitation analysis indicated recruitment of EPS8 to the CCNB1 and CDC25B promoters. Taken together, our findings support a novel partnering role of EPS8 with FOXM1 in the regulation of cancer cell proliferation and provides interesting insight into future design of therapeutic strategy to inhibit cancer cell proliferation

Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps

Peer reviewedPublisher PD

Rosa26-GFP Direct Repeat (RaDR-GFP) Mice Reveal Tissue- and Age-Dependence of Homologous Recombination in Mammals In Vivo

Homologous recombination (HR) is critical for the repair of double strand breaks and broken replication forks. Although HR is mostly error free, inherent or environmental conditions that either suppress or induce HR cause genomic instability. Despite its importance in carcinogenesis, due to limitations in our ability to detect HR in vivo, little is known about HR in mammalian tissues. Here, we describe a mouse model in which a direct repeat HR substrate is targeted to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR-GFP) mice, HR between two truncated EGFP expression cassettes can yield a fluorescent signal. In-house image analysis software provides a rapid method for quantifying recombination events within intact tissues, and the frequency of recombinant cells can be evaluated by flow cytometry. A comparison among 11 tissues shows that the frequency of recombinant cells varies by more than two orders of magnitude among tissues, wherein HR in the brain is the lowest. Additionally, de novo recombination events accumulate with age in the colon, showing that this mouse model can be used to study the impact of chronic exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating agent similar to the cancer chemotherapeutic temozolomide, shows that the colon, liver and pancreas are susceptible to DNA damage-induced HR. Finally, histological analysis of the underlying cell types reveals that pancreatic acinar cells and liver hepatocytes undergo HR and also that HR can be specifically detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model provides new understanding of how tissue and age impact susceptibility to HR, and enables future studies of genetic, environmental and physiological factors that modulate HR in mammals.National Institutes of Health (U.S.) (Program Project Grant P01-CA026731)National Institutes of Health (U.S.) (R33-CA112151)National Institute of Environmental Health Sciences (P30-ES002109)Singapore-MIT Alliance for Research and Technology CenterNational Institutes of Health (U.S.) (P41-EB015871)National Cancer Institute (U.S.) (P30-CA014051

Case Report: Patient with Hepatitis C, p-ANCA, and Cryoglobulin Antibodies Presenting with Necrotizing Crescentic p-ANCA Glomerulonephritis

Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in the United States, according to recent Center for Disease Control reports, and can have various renal manifestations. Cryoglobulins, antibodies that precipitate at colder temperatures in vitro, are a relatively common cause of renal disease in HCV infection. The cryoglobulin proteins can form occlusive aggregates in small glomerular capillary lumina or deposit in other areas of the glomerulus, resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The typical biopsy pattern is that of membranoproliferative glomerulonephritis (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti-neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected patients. In many reported cases, ANCA serologic testing may appear positive due to cross-reactivity of the immune assays; however, the biopsy findings do not support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the primary cause of glomerular injury. There are rare reports of microscopic polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies from these HCV-infected patients with concomitant MPA revealed a crescentic GN, associated with normal serum complement levels. We present a case of HCV-associated glomerular disease with the surprising biopsy finding of necrotizing and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in addition to the more typical lesions of MPGN or cryoglobulinemic GN

Postgraduate education for Chinese medicine practitioners: a Hong Kong perspective

<b>Background</b> Despite Hong Kong government's official commitment to the development of traditional Chinese medicine (TCM) over the last ten years, there appears to have been limited progress in public sector initiated career development and postgraduate training (PGT) for public university trained TCM practitioners. Instead, the private TCM sector is expected to play a major role in nurturing the next generation of TCM practitioners. In the present study we evaluated TCM graduates' perspectives on their career prospects and their views regarding PGT.<p></p> <b>Method</b> Three focus group discussions with 19 local TCM graduates who had worked full time in a clinical setting for fewer than 5 years. <p></p> <b>Results</b> Graduates were generally uncertain about how to develop their career pathways in Hong Kong with few postgraduate development opportunities; because of this some were planning to leave the profession altogether. Despite their expressed needs, they were dissatisfied with the current quality of local PGT and suggested various ways for improvement including supervised practice-based learning, competency-based training, and accreditation of training with trainee involvement in design and evaluation. In addition they identified educational needs beyond TCM, in particular a better understanding of western medicine and team working so that primary care provision might be more integrated in the future. <p></p> <b>Conclusion</b> TCM graduates in Hong Kong feel let down by the lack of public PGT opportunities which is hindering career development. To develop a new generation of TCM practitioners with the capacity to provide quality and comprehensive care, a stronger role for the government, including sufficient public funding, in promoting TCM graduates' careers and training development is suggested. Recent British and Australian experiences in prevocational western medicine training reform may serve as a source of references when relevant program for TCM graduates is planned in the futur

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

A labelled discrete choice experiment adds realism to the choices presented: preferences for surveillance tests for Barrett esophagus

<p>Abstract</p> <p>Background</p> <p>Discrete choice experiments (DCEs) allow systematic assessment of preferences by asking respondents to choose between scenarios. We conducted a labelled discrete choice experiment with realistic choices to investigate patients' trade-offs between the expected health gains and the burden of testing in surveillance of Barrett esophagus (BE).</p> <p>Methods</p> <p>Fifteen choice scenarios were selected based on 2 attributes: 1) type of test (endoscopy and two less burdensome fictitious tests), 2) frequency of surveillance. Each test-frequency combination was associated with its own realistic decrease in risk of dying from esophageal adenocarcinoma. A conditional logit model was fitted.</p> <p>Results</p> <p>Of 297 eligible patients (155 BE and 142 with non-specific upper GI symptoms), 247 completed the questionnaire (84%). Patients preferred surveillance to no surveillance. Current surveillance schemes of once every 1–2 years were amongst the most preferred alternatives. Higher health gains were preferred over those with lower health gains, except when test frequencies exceeded once a year. For similar health gains, patients preferred video-capsule over saliva swab and least preferred endoscopy.</p> <p>Conclusion</p> <p>This first example of a labelled DCE using realistic scenarios in a healthcare context shows that such experiments are feasible. A comparison of labelled and unlabelled designs taking into account setting and research question is recommended.</p

Attenuated IL-2 muteins leverage the TCR signal to enhance regulatory T cell homeostasis and response in vivo

Interleukin-2 (IL-2), along with T-cell receptor (TCR) signaling, are required to control regulatory T cell (Treg) homeostasis and function in vivo. Due to the heightened sensitivity to IL-2, Tregs retain the ability to respond to low-dose or attenuated forms of IL-2, as currently being developed for clinical use to treat inflammatory diseases. While attenuated IL-2 increases Treg selectivity, the question remains as to whether a weakened IL-2 signal sufficiently enhances Treg suppressive function(s) toward disease modification. To understand this question, we characterized the in vivo activity and transcriptomic profiles of two different attenuated IL-2 muteins in comparison with wildtype (WT) IL-2. Our study showed that, in addition to favoring Tregs, the attenuated muteins induced disproportionately robust effects on Treg activation and conversion to effector Treg (eTreg) phenotype. Our data furthermore suggested that Tregs activated by attenuated IL-2 muteins showed reduced dependence on TCR signal, at least in part due to the enhanced ability of IL-2 muteins to amplify the TCR signal in vivo. These results point to a new paradigm wherein IL-2 influences Tregs’ sensitivity to antigenic signal, and that the combination effect may be leveraged for therapeutic use of attenuated IL-2 muteins