119 research outputs found

    An evaluation of strategies used by the Landscapes and Policy Hub to achieve interdisciplinary and transdisciplinary research

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    The report presents an evaluation of the Landscapes and Policy Hub's approach to interdisciplinary and transdisciplinary research. The hub was a national, four year, $15 million collaborative research program. The focus of the evaluation was for researchers to reflect on the effectiveness of strategies used by the hub to facilitate interdisciplinarity (where researchers from different disciplines work together to solve problems) and transdisciplinarity (where researchers from different disciplines work in partnership with research users to solve problems). The evaluation was commissioned in the final phase of the hub’s life in the interests of improving performance of future interdisciplinary and transdisciplinary research. It was based on a number of strategies that had been implemented by the hub to encourage and facilitate interdisciplinary research occurring in partnership with research users. The aim of the evaluation was to improve performance of future interdisciplinary and transdisciplinary research. Six recommendations are presented

    The conservation value of human-modified landscapes for the world's primates

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    Land-use change pushes biodiversity into human-modified landscapes, where native ecosystems are surrounded by anthropic land covers (ALCs). Yet, the ability of species to use these emerging covers remains poorly understood. We quantified the use of ALCs by primates worldwide, and analyzed species' attributes that predict such use. Most species use secondary forests and tree plantations, while only few use human settlements. ALCs are used for foraging by at least 86 species with an important conservation outcome: those that tolerate heavily modified ALCs are 26% more likely to have stable or increasing populations than the global average for all primates. There is no phylogenetic signal in ALCs use. Compared to all primates on Earth, species using ALCs are less often threatened with extinction, but more often diurnal, medium or large-bodied, not strictly arboreal, and habitat generalists. These findings provide valuable quantitative information for improving management practices for primate conservation worldwide

    Novel M23 peptidases Pgp4, Pgp5, and Pgp6 contribute to helical cell shape in <em>Campylobacter jejuni</em>

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    Copyright \ua9 2025 Lin, Vermeulen, Biboy, Gaynor, Vollmer and Frirdich. The helical morphology of Campylobacter jejuni is maintained by its peptidoglycan (PG) layer and influences its success as a pathogen. Periplasmic PG hydrolases that cleave the PG glycan backbone and peptide sidechains (such as carboxypeptidases and endopeptidases) are critical for proper cell function and/or growth and are important in the PG remodeling required for cell shape generation and any morphological alterations. The C. jejuni shape is determined by PG hydrolases Pgp1 (DL-carboxypeptidase), Pgp2 (LD-carboxypeptidase) and Pgp3 (DD-carboxypeptidase/DD-endopeptidase), as well as a group of M23 peptidase domain containing proteins with previously uncharacterized activity: CJJ81176_1105, CJJ81176_1228, and CJJ81176_0166. Using a PG cleavage assay, we showed that 1105 and 1228 have DD-carboxypeptidase/DD-endopeptidase activity, and 0166 is a DD-carboxypeptidase. We renamed 1105, 1228, and 0166 to Pgp4 (peptidoglycan peptidase 4), Pgp5, and Pgp6, respectively. Pgp6 is the first described C. jejuni M23 peptidase with substrate selectivity on monomeric pentapeptides. Sequence comparisons between the DD-carboxypeptidase Pgp6 and the DD-carboxypeptidase/DD-endopeptidase Pgp3 (with an available crystal structure) and their corresponding orthologs revealed that Pgp6 contains insertion sequences in the M23 peptidase domain not present in Pgp3. Modeling of Pgp6 predicted that the insertion sequences would restrict the active site groove, only allowing entrance of a smaller substrate. This provides a possible explanation for the lack of Pgp6 DD-endopeptidase activity. To our knowledge, Pgp6 is the first reported DD-carboxypeptidase in the M23 peptidase superfamily. Deletions in pgp4, pgp5, and pgp6 resulted in mutants with varying curved rod morphologies and changes in PG muropeptide profiles in comparison to wild type and each other. Using these mutants, we examined the effect of deleting these genes on C. jejuni properties affecting pathogenesis and survival: motility, biofilm formation, autoagglutination, the ability to transition to a coccoid form, growth under varying pH, susceptibility to antimicrobial compounds, and adherence, invasion and intracellular survival in human epithelial cells. Each mutant showed distinct phenotypic changes to each other, indicating they are not functionally redundant. This also further supports the correlation between C. jejuni morphology and morphology-related genes with pathogenic potential

    Price effects of a hospital merger: Heterogeneity across health insurers, hospital products, and hospital locations

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    In most studies on hospital merger effects, the unit of observation is the merged hospital, whereas the observed price is the weighted average across hospital products and across payers. However, little is known about whether price effects vary between hospital locations, products, and payers. We expand existing bargaining models to allow for heterogeneous price effects and use a difference-in-differences model in which price changes at the merging hospitals are compared with price changes at comparison hospitals. We find evidence of heterogeneous price effects across health insurers, hospital products and hospital locations. These findings have implications for ex ante merger scrutiny

    Differential Carbohydrate Recognition by Campylobacter jejuni Strain 11168: Influences of Temperature and Growth Conditions

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    The pathogenic clinical strain NCTC11168 was the first Campylobacter jejuni strain to be sequenced and has been a widely used laboratory model for studying C. jejuni pathogenesis. However, continuous passaging of C. jejuni NCTC11168 has been shown to dramatically affect its colonisation potential. Glycan array analysis was performed on C. jejuni NCTC11168 using the frequently passaged, non-colonising, genome sequenced (11168-GS) and the infrequently passaged, original, virulent (11168-O) isolates grown or maintained under various conditions. Glycan structures recognised and bound by C. jejuni included terminal mannose, N-acetylneuraminic acid, galactose and fucose. Significantly, it was found that only when challenged with normal oxygen at room temperature did 11168-O consistently bind to sialic acid or terminal mannose structures, while 11168-GS bound these structures regardless of growth/maintenance conditions. Further, binding of un-capped galactose and fucosylated structures was significantly reduced when C. jejuni was maintained at 25°C under atmospheric oxygen conditions. These binding differences identified through glycan array analysis were confirmed by the ability of specific lectins to competitively inhibit the adherence of C. jejuni to a Caco-2 intestinal cell line. Our data suggests that the binding of mannose and/or N-acetylneuraminic acid may provide the initial interactions important for colonisation following environmental exposure

    Relevant Assay to Study the Adhesion of Plasmodium falciparum-Infected Erythrocytes to the Placental Epithelium

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    In placental malaria, Plasmodium falciparum-infected erythrocytes adhere to the apical plasma membrane of the placental epithelium, triggering an impairment of placental function detrimental to the fetus. The design of anti-adhesion intervention strategies requires a detailed understanding of the mechanisms involved. However, most adhesion assays lack in vivo relevance and are hardly quantitative. Here, we describe a flow cytometry-based adhesion assay that is fully relevant by using apical epithelial plasma membrane vesicles as the adhesion matrix, and being applicable to infected erythrocytes directly isolated from patients. Adhesion is measured both as the percentage of pathogens bound to epithelial membrane vesicles as well as the mean number of vesicles bound per infected erythrocytes. We show that adhesins alternative to those currently identified could be involved. This demonstrates the power of this assay to advance our understanding of epithelial adhesion of infected erythrocytes and in the design of intervention strategies

    Assessment of Surfactant Protein A (SP-A) dependent agglutination

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    Background: Monomers of the collectin surfactant associated protein-A (SP-A) are arranged in trimers and higher oligomers. The state of oligomerization differs between individuals and likely affects SP-A's functional properties. SP-A can form aggregates together with other SP-A molecules. Here we report and assess a test system for the aggregate forming properties of SP-A in serum and broncho-alveolar lavage samples. Methods: Anti-SP-A antibodies fixed to latex beads bound SP-A at its N-terminal end and allowed the interaction with other SP-A molecules in a given sample by their C-terminal carbohydrate recognition domain (CRD) to agglutinate the beads to aggregates, which were quantified by light microscopy. Results: SP-A aggregation was dependent on its concentration, the presence of calcium, and was dose-dependently inhibited by mannose. Unaffected by the presence of SP-D no aggregation was observed in absence of SP-A. The more complex the oligomeric structure of SP-A present in a particular sample, the better was its capability to induce aggregation at a given total concentration of SP-A. SP-A in serum agglutinated independently of the pulmonary disease; in contrast SP-A in lung lavage fluid was clearly inferior in patients with chronic bronchitis and particularly with cystic fibrosis compared to controls. Conclusions: The functional status of SP-A with respect to its aggregating properties in serum and lavage samples can be easily assessed. SP-A in lung lavage fluid in patients with severe neutrophilic bronchitis was inferior

    Quantitative Proteomics of Intracellular Campylobacter jejuni Reveals Metabolic Reprogramming

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    Campylobacter jejuni is the major cause of bacterial food-borne illness in the USA and Europe. An important virulence attribute of this bacterial pathogen is its ability to enter and survive within host cells. Here we show through a quantitative proteomic analysis that upon entry into host cells, C. jejuni undergoes a significant metabolic downshift. Furthermore, our results indicate that intracellular C. jejuni reprograms its respiration, favoring the respiration of fumarate. These results explain the poor ability of C. jejuni obtained from infected cells to grow under standard laboratory conditions and provide the bases for the development of novel anti microbial strategies that would target relevant metabolic pathways

    Universal high work function flexible anode for simplified ITO-free organic and perovskite light-emitting diodes with ultra-high efficiency

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    Flexible transparent electrode materials such as conducting polymers, silver nanowires, carbon nanotubes and graphenes are being investigated as possible replacements for conventional brittle inorganic electrodes. However, they have critical drawbacks of low work function (WF), resulting in a high hole injection barrier to an overlying semiconducting layer in simplified organic or organic-inorganic hybrid perovskite light-emitting diodes (OLEDs or PeLEDs). Here, we report a new anode material (AnoHIL) that has multifunction of both an anode and a hole injection layer (HIL) as a single layer. The AnoHIL has easy WF tunability up to 5.8 eV and thus makes ohmic contact without any HIL. We applied our anodes to simplified OLEDs, resulting in very high efficiency (62% ph el(-1) for single and 88% ph el(-1) for tandem). The AnoHIL showed a similar tendency in simplified PeLEDs, implying universal applicability to various optoelectronics. We also demonstrated large-area flexible lightings using our anodes. Our results provide a significant step toward the next generation of high-performance simplified indium tin oxide (ITO)-free light-emitting diodes.

    Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

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    <p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p
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