Ligand-receptor binding kinetics in surface plasmon resonance cells: A Monte Carlo analysis

Surface plasmon resonance (SPR) chips are widely used to measure association and dissociation rates for the binding kinetics between two species of chemicals, e.g., cell receptors and ligands. It is commonly assumed that ligands are spatially well mixed in the SPR region, and hence a mean-field rate equation description is appropriate. This approximation however ignores the spatial fluctuations as well as temporal correlations induced by multiple local rebinding events, which become prominent for slow diffusion rates and high binding affinities. We report detailed Monte Carlo simulations of ligand binding kinetics in an SPR cell subject to laminar flow. We extract the binding and dissociation rates by means of the techniques frequently employed in experimental analysis that are motivated by the mean-field approximation. We find major discrepancies in a wide parameter regime between the thus extracted rates and the known input simulation values. These results underscore the crucial quantitative importance of spatio-temporal correlations in binary reaction kinetics in SPR cell geometries, and demonstrate the failure of a mean-field analysis of SPR cells in the regime of high Damk\"ohler number Da > 0.1, where the spatio-temporal correlations due to diffusive transport and ligand-receptor rebinding events dominate the dynamics of SPR systems.Comment: 21 pages, 9 figure

Achieving impact from ecosystem assessment and valuation of urban greenspace: The case of i-Tree Eco in Great Britain

Numerous tools have been developed to assist environmental decision-making, but there has been little examination of whether these tools achieve this aim, particularly for urban environments. This study aimed to evaluate the use of the i-Tree Eco tool in Great Britain, an assessment tool developed to support urban forest management. The study employed a documentary review, an online survey, and interviews in six case study areas to examine five impacts (instrumental, conceptual, capacity-building, enduring connectivity, and culture/attitudes towards knowledge exchange) and to identify which factors inhibited or supported achievement of impact. It revealed that the i-Tree Eco projects had helped to increase knowledge of urban forests and awareness of the benefits they provide. While there was often broad use of i-Tree Eco findings in various internal reports, external forums, and discussions of wider policies and plans, direct changes relating to improved urban forest management, increased funding or new tree policies were less frequent. The barriers we identified which limited impact included a lack of project champions, policy drivers and resources, problems with knowledge transfer and exchange, organisational and staff change, and negative views of trees. Overall, i-Tree Eco, similar to other environmental decision-making tools, can help to improve the management of urban trees when planned as one step in a longer process of engagement with stakeholders and development of new management plans and policies. In this first published impact evaluation of multiple i-Tree Eco projects, we identified eight lessons to enhance the impact of future i-Tree Eco projects, transferable to other environmental decision-making tools

Tree insect pests and pathogens: a global systematic review of their impacts in urban areas

Trees contribute greatly to urban environments and human well-being, yet relatively little is known about the extent to which a rising incidence of tree insect pests and pathogens may be affecting these contributions. To address this issue, we undertook a systematic review and synthesis of the diverse global empirical evidence on the impacts of urban tree insect pests and pathogens, using bibliographic databases. Following screening and appraisal of over 3000 articles from a wide range of fields, 100 studies from 28 countries, spanning 1979–2021, were conceptually sorted into a three-part framework: (1) environmental impacts, representing 95 of the studies, including those reporting on tree damage, mortality, reduced growth, and changes in tree function; (2) social impacts were reported by 35 of studies, including on aesthetics, human health, and safety hazards; and (3) economic impacts, reported in 24 of studies, including on costs of pest management, and economic losses. There has been a considerable increase in urban impact studies since 2011. Evidence gaps exist on impacts on climate-regulating capacity, including temperature regulation, water retention, soil erosion, and wind protection, but also on specific hazards, nuisances, human well-being, property damages, and hazard liabilities. As a knowledge synthesis, this article presents the best available evidence of urban tree insect / pathogen impacts to guide policy, management and further research. It will enable us to better forecast how growing threats will affect the urban forest and plan for these eventualities

Correction: Large cortical bone pores in the tibia are associated with proximal femur strength

[This corrects the article DOI: 10.1371/journal.pone.0215405.

Clustering of antibiotic resistance of E. coli in couples: suggestion for a major role of conjugal transmission

BACKGROUND: Spread of antibiotic resistance in hospitals is a well-known problem, but studies investigating the importance of factors potentially related to the spread of resistant bacteria in outpatients are sparse. METHODS: Stool samples were obtained from 206 healthy couples in a community setting in Southern Germany in 2002–2003. E. coli was cultured and minimal inhibition concentrations were tested. Prevalences of E. coli resistance to commonly prescribed antibiotics according to potential risk factors were ascertained. RESULTS: Prevalences of ampicillin resistance were 15.7% and 19.4% for women and men, respectively. About ten percent and 15% of all isolates were resistant to cotrimoxazole and doxycycline, respectively. A partner carrying resistance was the main risk factor for being colonized with resistant E. coli. Odds ratios (95% CI) for ampicillin and cotrimoxazole resistance given carriage of resistant isolates by the partner were 6.9 (3.1–15.5) and 3.3 (1.5–18.0), respectively. CONCLUSION: Our data suggest that conjugal transmission may be more important for the spread of antibiotic resistance in the community setting than commonly suspected risk factors such as previous antibiotic intake or hospital contacts

Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic β cells

Insulin resistance, hyperinsulinemia, and hyperproinsulinemia occur early in the pathogenesis of type 2 diabetes (T2D). Elevated levels of proinsulin and proinsulin intermediates are markers of β-cell dysfunction and are strongly associated with development of T2D in humans. However, the mechanism(s) underlying β-cell dysfunction leading to hyperproinsulinemia is poorly understood. Here, we show that disruption of insulin receptor (IR) expression in β cells has a direct impact on the expression of the convertase enzyme carboxypeptidase E (CPE) by inhibition of the eukaryotic translation initiation factor 4 gamma 1 translation initiation complex scaffolding protein that is mediated by the key transcription factors pancreatic and duodenal homeobox 1 and sterol regulatory element-binding protein 1, together leading to poor proinsulin processing. Reexpression of IR or restoring CPE expression each independently reverses the phenotype. Our results reveal the identity of key players that establish a previously unknown link between insulin signaling, translation initiation, and proinsulin processing, and provide previously unidentified mechanistic insight into the development of hyperproinsulinemia in insulin-resistant states

In Vivo Conditional Pax4 Overexpression in Mature Islet β-Cells Prevents Stress-Induced Hyperglycemia in Mice

OBJECTIVE To establish the role of the transcription factor Pax4 in pancreatic islet expansion and survival in response to physiological stress and its impact on glucose metabolism, we generated transgenic mice conditionally and selectively overexpressing Pax4 or a diabetes-linked mutant variant (Pax4R129 W) in β-cells. RESEARCH DESIGN AND METHODS Glucose homeostasis and β-cell death and proliferation were assessed in Pax4- or Pax4R129 W-overexpressing transgenic animals challenged with or without streptozotocin. Isolated transgenic islets were also exposed to cytokines, and apoptosis was evaluated by DNA fragmentation or cytochrome C release. The expression profiles of proliferation and apoptotic genes and β-cell markers were studied by immunohistochemistry and quantitative RT-PCR. RESULTS Pax4 but not Pax4R129 W protected animals against streptozotocin-induced hyperglycemia and isolated islets from cytokine-mediated β-cell apoptosis. Cytochrome C release was abrogated in Pax4 islets treated with cytokines. Interleukin-1β transcript levels were suppressed in Pax4 islets, whereas they were increased along with NOS2 in Pax4R129 W islets. Bcl-2, Cdk4, and c-myc expression levels were increased in Pax4 islets while MafA, insulin, and GLUT2 transcript levels were suppressed in both animal models. Long-term Pax4 expression promoted proliferation of a Pdx1-positive cell subpopulation while impeding insulin secretion. Suppression of Pax4 rescued this defect with a concomitant increase in pancreatic insulin content. CONCLUSIONS Pax4 protects adult islets from stress-induced apoptosis by suppressing selective nuclear factor-κB target genes while increasing Bcl-2 levels. Furthermore, it promotes dedifferentiation and proliferation of β-cells through MafA repression, with a concomitant increase in Cdk4 and c-myc expression