Honey bee virus research is an enormously broad area, ranging from subcellular molecular biology through physiology and behaviour, to individual and colony-level symptoms, transmission and ...epidemiology. The research methods used in virology are therefore equally diverse. This article covers those methods that are very particular to virological research in bees, with numerous cross-referrals to other BEEBOOK papers on more general methods, used in virology as well as other research. At the root of these methods is the realization that viruses at their most primary level inhabit a molecular, subcellular world, which they manipulate and interact with, to produce all higher order phenomena associated with virus infection and disease. Secondly, that viruses operate in an exponential world, while the host operates in a linear world and that much of the understanding and management of viruses hinges on reconciling these fundamental mathematical differences between virus and host. The article concentrates heavily on virus propagation and methods for detection, with minor excursions into surveying, sampling management and background information on the many viruses found in bees.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
AbstractObjectivesTo describe neurodevelopment at age 5 among children born preterm.DesignPopulation based cohort study, EPIPAGE-2.SettingFrance, 2011.Participants4441 children aged 5½ born at 24-26, ...27-31, and 32-34 weeksMain outcome measuresSevere/moderate neurodevelopmental disabilities, defined as severe/moderate cerebral palsy (Gross Motor Function Classification System (GMFCS) ≥2), or unilateral or bilateral blindness or deafness, or full scale intelligence quotient less than minus two standard deviations (Wechsler Preschool and Primary Scale of Intelligence, 4th edition). Mild neurodevelopmental disabilities, defined as mild cerebral palsy (GMFCS-1), or visual disability ≥3.2/10 and <5/10, or hearing loss <40 dB, or full scale intelligence quotient (minus two to minus one standard deviation) or developmental coordination disorders (Movement Assessment Battery for Children, 2nd edition, total score less than or equal to the fifth centile), or behavioural difficulties (strengths and difficulties questionnaire, total score greater than or equal to the 90th centile), school assistance (mainstream class with support or special school), complex developmental interventions, and parents’ concerns about development. The distributions of the scores in contemporary term born children were used as reference. Results are given after multiple imputation as percentages of outcome measures with exact binomial 95% confidence intervals.ResultsAmong 4441 participants, 3083 (69.4%) children were assessed. Rates of severe/moderate neurodevelopmental disabilities were 28% (95% confidence interval 23.4% to 32.2%), 19% (16.8% to 20.7%), and 12% (9.2% to 14.0%) and of mild disabilities were 38.5% (33.7% to 43.4%), 36% (33.4% to 38.1%), and 34% (30.2% to 37.4%) at 24-26, 27-31, and 32-34 weeks, respectively. Assistance at school was used by 27% (22.9% to 31.7%), 14% (12.1% to 15.9%), and 7% (4.4% to 9.0%) of children at 24-26, 27-31, and 32-34 weeks, respectively. About half of the children born at 24-26 weeks (52% (46.4% to 57.3%)) received at least one developmental intervention which decreased to 26% (21.8% to 29.4%) for those born at 32-34 weeks. Behaviour was the concern most commonly reported by parents. Rates of neurodevelopment disabilities increased as gestational age decreased and were higher in families with low socioeconomic status.ConclusionsIn this large cohort of children born preterm, rates of severe/moderate neurodevelopmental disabilities remained high in each gestational age group. Proportions of children receiving school assistance or complex developmental interventions might have a significant impact on educational and health organisations. Parental concerns about behaviour warrant attention.
Abstract Objectives The purpose of this study was to investigate the effect of light-curing protocol on degree of conversion (DC), volume contraction ( C ), elastic modulus ( E ), and glass ...transition temperature ( Tg ) as measured on a model polymer. It was a further aim to correlate the measured values with each other. Methods Different light-curing protocols were used in order to investigate the influence of energy density (ED), power density (PD), and mode of cure on the properties. The modes of cure were continuous, pulse-delay, and stepped irradiation. DC was measured by Raman micro-spectroscopy. C was determined by pycnometry and a density column. E was measured by a dynamic mechanical analyzer (DMA), and Tg was measured by differential scanning calorimetry (DSC). Data were submitted to two- and three-way ANOVA, and linear regression analyses. Results ED, PD, and mode of cure influenced DC, C , E , and Tg of the polymer. A significant positive correlation was found between ED and DC ( r = 0.58), ED and E ( r = 0.51), and ED and Tg ( r = 0.44). Taken together, ED and PD were significantly related to DC and E . The regression coefficient was positive for ED and negative for PD. Significant positive correlations were detected between DC and C ( r = 0.54), DC and E ( r = 0.61), and DC and Tg ( r = 0.53). Comparisons between continuous and pulse-delay modes of cure showed significant influence of mode of cure: pulse-delay curing resulted in decreased DC, decreased C , and decreased Tg . Influence of mode of cure, when comparing continuous and step modes of cure, was more ambiguous. Significance A complex relationship exists between curing protocol, microstructure of the resin and the investigated properties. The overall performance of a composite is thus indirectly affected by the curing protocol adopted, and the desired reduction of C may be in fact a consequence of the decrease in DC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The cation-independent mannose 6-phosphate receptor (CI-M6PR) is a ubiquitous transmembrane receptor whose main intracellular role is to direct enzymes carrying mannose 6-phosphate moieties to ...lysosomal compartments. Recently, the small membrane-bound portion of this receptor has appeared to be implicated in numerous pathophysiological processes. This review presents an overview of the main ligand partners and the roles of CI-M6PR in lysosomal storage diseases, neurology, immunology and cancer fields. Moreover, this membrane receptor has already been noted for its strong potential in therapeutic applications thanks to its cellular internalization activity and its ability to address pathogenic factors to lysosomes for degradation. A number of therapeutic delivery approaches using CI-M6PR, in particular with enzymes, antibodies or nanoparticles, are currently being proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
CD123, the alpha chain of the IL-3 receptor, is an attractive target for acute myeloid leukemia (AML) treatment. However, cytotoxic antibodies or T cell engagers targeting CD123 had insufficient ...efficacy or safety in clinical trials. We show that expression of CD64, the high-affinity receptor for human IgG, on AML blasts confers resistance to anti-CD123 antibody-dependent cell cytotoxicity (ADCC) in vitro. We engineer a trifunctional natural killer cell engager (NKCE) that targets CD123 on AML blasts and NKp46 and CD16a on NK cells (CD123-NKCE). CD123-NKCE has potent antitumor activity against primary AML blasts regardless of CD64 expression and induces NK cell activation and cytokine secretion only in the presence of AML cells. Its antitumor activity in a mouse CD123
tumor model exceeds that of the benchmark ADCC-enhanced antibody. In nonhuman primates, it had prolonged pharmacodynamic effects, depleting CD123
cells for more than 10 days with no signs of toxicity and very low inflammatory cytokine induction over a large dose range. These results support clinical development of CD123-NKCE.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Background
The benefits of systematic re-excision (RE) after initial unplanned excision (UE) of soft tissue sarcoma (STS) are unknown.
Objective
The aim of this study was to evaluate the impact of ...delayed RE versus systematic RE after UE on overall survival (OS), metastatic relapse-free survival (MRFS), local relapse-free survival (LRFS), and rate of amputation.
Methods
Patients who underwent complete UE, without metastasis or residual disease, for primary extremity or superficial STS between 2007 and 2013 were analyzed. The amputation rate, LRFS, MRFS, and OS were assessed in cases of systematic RE in sarcoma referral centers (Group A), systematic RE outside of community centers (Group B), or without RE (Group C).
Results
Groups A, B, and C included 300 (48.2%), 71 (11.4%), and 251 (40.4%) patients, respectively. Median follow-up was 61 months and 5-year OS was 88.4%, 87.3%, and 88% in Groups A, B, and C, respectively (
p
= 0.22), while 5-year MFRS was 85.4%, 86.2%, and 84.9%, respectively (
p
= 0.938); RE (
p
= 0.55) did not influence MRFS. The 5-year LRFS was 83%, 73.5%, and 63.8% in Groups A, B and C, respectively (
p
= 0.00001). Of the 123 local recurrences observed, 0/28, 1/15, and 5/80 patients in Groups A, B, and C, respectively, required amputation (
p
= 0.41). Factors influencing LRFS were adjuvant radiotherapy hazard ratio (HR) 0.21;
p
= 0.0001, initial R0 resection (HR 0.24,
p
= 0.0001), and Group A (HR 0.44;
p
= 0.01).
Conclusion
Systematic RE in sarcoma centers offers best local control but does not impact OS. Delayed RE at the time of local relapse, if any, could be an option.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Arctic Indigenous Peoples are among the most exposed humans when it comes to foodborne mercury (Hg). In response, Hg monitoring and research have been on-going in the circumpolar Arctic since about ...1991; this work has been mainly possible through the involvement of Arctic Indigenous Peoples. The present overview was initially conducted in the context of a broader assessment of Hg research organized by the Arctic Monitoring and Assessment Programme. This article provides examples of Indigenous Peoples' contributions to Hg monitoring and research in the Arctic, and discusses approaches that could be used, and improved upon, when carrying out future activities. Over 40 mercury projects conducted with/by Indigenous Peoples are identified for different circumpolar regions including the U.S., Canada, Greenland, Sweden, Finland, and Russia as well as instances where Indigenous Knowledge contributed to the understanding of Hg contamination in the Arctic. Perspectives and visions of future Hg research as well as recommendations are presented. The establishment of collaborative processes and partnerships/co-production approaches with scientists and Arctic Indigenous Peoples, using good communication practices and transparency in research activities, are key to the success of research and monitoring activities in the Arctic. Sustainable funding for community-driven monitoring and research programs in Arctic countries would be beneficial and assist in developing more research/monitoring capacity and would promote a more holistic approach to understanding Hg in the Arctic. These activities should be well connected to circumpolar/international initiatives to ensure broader availability of the information and uptake in policy development.
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•Indigenous Peoples greatly contribute to Arctic Hg research and monitoring•Insights into key involvement of Indigenous Peoples in Hg study are provided•Over 40 examples of Hg research conducted with/by Indigenous Peoples are presented•Indigenous Knowledge in research and decision-making is being increasingly recognized•Co-production approaches of scientists and Indigenous Peoples in research are key
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Extracellular vesicles production and their use for downstream applications.•Cell-surface membrane protein interaction studies using extracellular vesicles.•Extracellular vesicles as ...a tool for membrane protein structure determination.•Extracellular vesicles use for immunization and antibody generation.
Producing intact recombinant membrane proteins for structural studies is an inherently challenging task due to their requirement for a cell-lipid environment. Most of the procedures developed involve isolating the protein by solubilization with detergent and further reconstitutions into artificial membranes. These procedures are highly time consuming and suffer from further drawbacks, including low yields and high cost.
We describe here an alternative method for rapidly obtaining recombinant cell-surface membrane proteins displayed on extracellular vesicles (EVs) derived from cells in culture. Interaction between these membrane proteins and ligands can be analyzed directly on EVs. Moreover, EVs can also be used for protein structure determination or immunization purposes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This article discusses the uncertainty about water quality in the Province of Chacabuco (Santiago Metropolitan Region) in Chile, a region marked by very strong pressure on the resource, both natural ...(drought) and anthropogenic (urban growth, agricultural intensification, industrialisation, and mining activity). Our main objective was, through an interdisciplinary research approach, to understand how the uncertainty concerning the state of hydro systems becomes central in the social representations of the inhabitants, since there is no consensus amongst regional stakeholders about environmental impacts nor is there evidence of pollution. By cross-referencing geochemical data on water quality and the inhabitants’ discourse on the resource, we identified those factors that create uncertainty about water resources: institutional lack of knowledge of the state of the resource, scientific difficulties in understanding the functioning of the hydro system, water and ground quality data that are difficult to interpret given the persistent drought, and the inhabitants’ distrust of data producers, in a context of planned regulatory zoning of polluting activities in the area. We also show the negative effects that the lack of trustworthy information has on the daily lives of local communities living near industrial infrastructures: anxiety, health concerns, and mistrust of drinking water, even though it is potable.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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