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High-pathogenicity avian influenza viruses continue to circulate in poultry and wild birds and occasionally infect humans, sometimes with fatal outcomes. Development of vaccines is a priority to prepare for potential pandemics but is complicated by antigenic variation of the surface glycoprotein hemagglutinin. We report the immunological profile induced by human immunization with modified vaccinia virus Ankara (MVA) expressing the hemagglutinin gene of influenza A(H5N1) virus A/Vietnam/1194/04 (rMVA-H5). In a double-blinded phase 1/2a clinical trial, 79 individuals received 1 or 2 injections of rMVA-H5 or vector control. Twenty-seven study subjects received a booster immunization after 1 year. The breadth, magnitude, and properties of vaccine-induced antibody and T-cell responses were characterized. rMVA-H5 induced broadly reactive antibody responses, demonstrated by protein microarray, hemagglutination inhibition, virus neutralization, and antibody-dependent cellular cytotoxicity assays. Antibodies cross-reacted with antigenically distinct H5 viruses, including the recently emerged subtypes H5N6 and H5N8 and the currently circulating subtype H5N1. In addition, the induction of T cells specific for H5 viruses of 2 different clades was demonstrated. rMVA-H5 induced immune responses that cross-reacted with H5 viruses of various clades. These findings validate rMVA-H5 as vaccine candidate against antigenically distinct H5 viruses. NTR3401.

Extra-epitopic amino acid residues affect recognition of human influenza A viruses (IAVs) by CD8+ T-lymphocytes (CTLs) specific for the highly conserved HLA-A*0201 restricted M158-66 epitope located in the matrix 1 (M1) protein. These residues are absent in the M1 protein of the 2009-pandemic IAV (H1N1pdm09). Consequently, stimulation with M1 protein of H1N1pdm09 IAV resulted in stronger activation and lytic activity of M158-66-specific CTLs than stimulation with seasonal H3N2 IAVs. During >6 years of circulation in the human population, descendants of the H1N1pdm09 virus had accumulated 4 other amino acid substitutions. However, these did not affect M158-66-specific CTL activation.

In late December 2019, a cluster of cases of pneumonia of unknown etiology were reported linked to a market in Wuhan, China 1 . The causative agent was identified as the species Severe acute respiratory syndrome-related coronavirus and was named SARS-CoV-2 (ref.  2 ). By 16 April the virus had spread to 185 different countries, infected over 2,000,000 people and resulted in over 130,000 deaths 3 . In the Netherlands, the first case of SARS-CoV-2 was notified on 27 February. The outbreak started with several different introductory events from Italy, Austria, Germany and France followed by local amplification in, and later also outside, the south of the Netherlands. The combination of near to real-time whole-genome sequence analysis and epidemiology resulted in reliable assessments of the extent of SARS-CoV-2 transmission in the community, facilitating early decision-making to control local transmission of SARS-CoV-2 in the Netherlands. We demonstrate how these data were generated and analyzed, and how SARS-CoV-2 whole-genome sequencing, in combination with epidemiological data, was used to inform public health decision-making in the Netherlands. The combination of near to real-time whole-genome sequence analysis and epidemiology resulted in reliable assessments of the extent of SARS-CoV-2 transmission in the community, facilitating early decision-making to control local transmission of SARS-CoV-2 in the Netherlands.

Candidatus Accumulibacter phosphatis is an important microorganism for enhanced biological phosphorus removal (EBPR). In a previous study, we found a remarkable flexibility regarding salinity, since this same microorganism could thrive in both freshwater- and seawater-based environments, but the mechanism for the tolerance to saline conditions remained unknown. Here, we identified and described the role of trehalose as an osmolyte in Ca. Accumulibacter phosphatis. A freshwater-adapted culture was exposed to a single batch cycle of hyperosmotic and hypo-osmotic shock, which led to the release of trehalose up to 5.34 mg trehalose/g volatile suspended solids (VSS). Long-term adaptation to 30% seawater-based medium in a sequencing batch reactor (SBR) gave a stable operation with complete anaerobic uptake of acetate and propionate along with phosphate release of 0.73 Pmol/Cmol, and complete aerobic uptake of phosphate. Microbial analysis showed Ca. Accumulibacter phosphatis clade I as the dominant organism in both the freshwater- and seawater-adapted cultures (> 90% presence). Exposure of the seawater-adapted culture to a single batch cycle of hyperosmotic incubation and hypo-osmotic shock led to an increase in trehalose release upon hypo-osmotic shock when higher salinity is used for the hyperosmotic incubation. Maximum trehalose release upon hypo-osmotic shock was achieved after hyperosmotic incubation with 3× salinity increase relative to the salinity in the SBR adaptation reactor, resulting in the release of 11.9 mg trehalose/g VSS. Genome analysis shows the possibility of Ca. Accumulibacter phosphatis to convert glycogen into trehalose by the presence of treX, treY, and treZ genes. Addition of trehalose to the reactor led to its consumption, both during anaerobic and aerobic phases. These results indicate the flexibility of the metabolism of Ca. Accumulibacter phosphatis towards variations in salinity.Key points• Trehalose is identified as an osmolyte in Candidatus Accumulibacter phosphatis.• Ca. Accumulibacter phosphatis can convert glycogen into trehalose.• Ca. Accumulibacter phosphatis clade I is present and active in both seawater and freshwater.

Cardiometabolic risk (CMR), also known as metabolic syndrome or insulin resistance syndrome, comprises obesity (particularly central or abdominal obesity), high triglycerides, low HDL, elevated blood pressure, and elevated plasma glucose. Leading to death from diabetes, heart disease, and stroke, the root cause of CMR is inadequate physical activity, a Western diet identified primarily by low intake of fruits, vegetables, and whole grains, and high in saturated fat, as well as a number of yet-to-be-identified genetic factors. While the pathophysiological pathways related to CMR are complex, the universal need for adequate physical activity and a diet that emphasizes fruits and vegetables and whole grains, while minimizing food high in added sugars and saturated fat suggests that these behaviors are the appropriate focus of intervention.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

This investigation estimates the impact of ten modifiable health risk behaviors and measures and their impact on health care expenditures, controlling for other measured risk and demographic factors. Retrospective two-stage multivariate analyses, including logistic and linear regression models, were used to follow up 46,026 employees from six large health care purchasers for up to 3 years after they completed an initial health risk appraisal. These participants contributed 113,963 person-years of experience. Results show that employees at high risk for poor health outcomes had significantly higher expenditures than did subjects at lower risk in seven often risk categories: those who reported themselves as depressed (70% higher expenditures), at high stress (46%), with high blood glucose levels (35%), at extremely high or low body weight (21%), former (20%) and current (14%) tobacco users, with high blood pressure (12%), and with sedentary lifestyle (10%). These same risk factors were found to be associated with a higher likelihood of having extremely high (outlier) expenditures. Employees with multiple risk profiles for specific disease outcomes had higher expenditures than did those without these profiles for the following diseases: heart disease (228% higher expenditures), psychosocial problems (147%), and stroke (85%). Compared with prior studies, the results provide more precise estimates of the incremental medical expenditures associated with common modifiable risk factors after we controlled for multiple risk conditions and demographic confounders. The authors conclude that common modifiable health risks are associated with short-term increases in the likelihood of incurring health expenditures and in the magnitude of those expenditures.

Granular sludge intensifies the removal of nutrients from wastewater. Granules structured by extracellular polymeric substances (EPS) can be recovered as biomaterial. Links between microbial selection and EPS formation during granulation need to get uncovered. We inoculated anaerobic-aerobic sequencing batch reactors with either flocs or granules to study the relationships between microbial selection, bioaggregation, exopolymer formation, and EPS composition. Selection for slow-growing organisms like the model polyphosphate- accumulating organism “Candidatus Accumulibacter” (max. 83% vs. amplicon sequencing read counts) and glycogen-accumulating organism “Ca. Competibacter” (max. 45%) sustained granulation. Gel-forming exopolymers were produced as high as above 40% of the volatile solids of the biomass by stepwise increase of the organic loading rate (0.3 to 2.0 g CODAc d-1 LR-1). Confocal laser scanning microscopy, FT-IR spectroscopy, and HPAE-PAD chromatography revealed the complex and dynamic chemical compositions of the structural EPS in relation to microbial population shifts along reactor regimes. The analysis of 20 representative genomes of “Ca. Accumulibacter” and “Ca. Competibacter” recovered from public databases revealed their functional potential to produce EPS among other representative wastewater microorganisms. The more than 40 functional gene categories annotated highlight the complexity of EPS metabolic networks from monomers processing to assembly, export, and epimerizations. The combination of ecological engineering principles and systems microbiology will help unravel and direct the production of EPS from wastewater, valorizing residual granular sludge into beneficial biomaterials for the circular economy. Selection for slow-growing organisms like PAOs and GAOs fostered a robust granulation. Structural EPS were produced above 40% of biomass volatile content under high loading. Chemical composition of EPS evolved together with the microbial community composition. Genomic insights highlighted the genetic potential of PAOs and GAOs for EPS formation. Microbial communities are complex; further are their EPS compositions and metabolisms.