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This review article analyzes factors affecting emergency response to hazardous events on highways and their bridges, with focus on man-made and natural scenarios: heavy vehicle collision with a bridge, earthquake, heavy snowfall, and flooding. For each disaster scenario, selected historical events were compiled to determine influential factors and success criteria for efficient emergency response, both related to organizational and technical measures. This study constituted a part of a resilience management process, recently developed and demonstrated within the European Union (EU)-funded H2020 project IMPROVER and can be a useful approach in aiding operators of transportation infrastructure to improve their resilience to emergency incidents.

During Lotus japonicus-Mesorhizobium loti symbiosis, the LOTUS HISTIDINE KINASE1 (LHK1) cytokinin receptor regulates both the initiation of nodule formation and the scope of root infection. However, the exact spatiotemporal mechanism by which this receptor exerts its symbiotic functions has remained elusive. In this study, we performed cell type-specific complementation experiments in the hyperinfected lhk1-1 mutant background, targeting LHK1 to either the root epidermis or the root cortex. We also utilized various genetic backgrounds to characterize expression of several genes regulating symbiotic infection. We show here that expression of LHK1 in the root cortex is required and sufficient to regulate both nodule formation and epidermal infections. The LHK1-dependent signalling that restricts subsequent infection events is triggered before initial cell divisions for nodule primordium formation. We also demonstrate that AHK4, the Arabidopsis orthologue of LHK1, is able to regulate M. loti infection in L. japonicus, suggesting that an endogenous cytokinin receptor could be sufficient for engineering nitrogen-fixing root nodule symbiosis in nonlegumes. Our data provide experimental evidence for the existence of an LHK1-dependent root cortex-to-epidermis feedback mechanism regulating rhizobial infection. This root-localized regulatory module functionally links with the systemic autoregulation of nodulation (AON) to maintain the homeostasis of symbiotic infection., (© 2019 Her Majesty the Queen in Right of Canada as represented by the Minister of Agriculture and Agri-Food New Phytologist © 2019 New Phytologist Trust.)

Background: Short regulating RNAs guide many cellular processes. Compared with transcription factor proteins they appear to provide more specialized control and their deletions are less frequently lethal., Results: We find large differences between computationally predicted lists of human microRNA (miRNA)-target pairs. Instead of integrating these lists we use the two most accurate of them. Next, we construct the co-regulation network of human miRNAs as nodes by computing the correlation (link weight) between the gene silencing scores of individual miRNAs. In this network, we locate groups of tightly co-regulating nodes (modules). Despite explicitly allowing overlaps the co-regulation modules of miRNAs are well separated. We use the modules and miRNA co-expression data to define and compute miRNA essentiality. Instead of focusing on particular biological functions we identify a miRNA as essential, if it has a low co-expression with the miRNAs in its module. This may be thought of as having many workers performing the same tasks together in one place (non-essential miRNAs) as opposed to a single worker performing those tasks alone (essential miRNA)., Conclusions: On the system level, we quantitatively confirm previous findings about the specialized control provided by miRNAs. For knock-out tests we list the groups of our predicted most and least essential miRNAs. In addition, we provide possible explanations for (i) the low number of individually essential miRNAs in Caenorhabdtits elegans and (ii) the high number of ubiquitous miRNAs influencing cell and tissue-specific miRNA expression patterns in mouse and human.

Over the past decade much research has focused on understanding the molecular pathways that regulate the development of a tumor-associated vasculature. In 1999, Lyden and colleagues showed that mice deficient in one to three Id1 or Id3 alleles could not support the growth of tumor xenografts due to defects in tumor-associated angiogenesis. Three recently published manuscripts have now re-examined the role of Id genes in the development of a tumor-associated vasculature using more clinically relevant tumor model systems. Remarkably, all three studies have found strikingly different results compared to the original xenograft data published in 1999. Below we review the current understanding of the role of Id genes in the development of a tumor-associated vasculature given the most recent data and suggest ways in which animal tumor model systems might be put to better use to provide more clinically relevant information.

Background: Leflunomide, an inhibitor of protein kinase activity and pyrimidine synthesis, is an experimental immunosuppressive agent effective in the prevention/control of acute and chronic rejection in animal models and currently in phase I clinical trials in human transplant recipients. This agent is also effective in the control of graft-versus-host disease, autoimmune reactions, and the growth of certain tumors. The importance of the endothelium in these disease processes led us to hypothesize that leflunomide might act directly upon the endothelial cell (EC)., Methods and Results: Assay of human EC colony formation demonstrated dose-dependent, leflunomide-mediated inhibition of EC proliferation. In addition, the organization of EC into capillary-like networks, which occurs during 18 hr of incubation on Matrigel, was progressively disrupted with increasing concentrations of leflunomide. Finally, fibrin-embedded transverse sections of murine aorta, which sprout numerous microvessels during an 11-day incubation, were inhibited from doing so in the presence of this agent. All drug concentrations used in these experiments were nontoxic and pharmacologically relevant, and none of these effects were reversible by exogenous uridine, implying that inhibition of these processes was not due to intracellular pyrimidine depletion. Furthermore, neither cyclosporine nor tacrolimus exerted inhibitory activity in any of the experiments described above., Conclusions: Data generated by these studies distinguish leflunomide among immunosuppressants as uniquely capable of inhibiting angiogenesis-related endothelial functions and suggest additional mechanisms by which this agent might intervene in the diverse array of disease processes against which it has shown therapeutic potential.

The effects of intracarotid infusions of beta-amyloid (1-42) peptide was studied on the permeability of brain vessels. Using a quantitative Evans blue method a dose-dependent increase of brain tissue albumin content was established following intracarotid injections of the peptide. Cerebral vessels of increased permeability were also demonstrated with a vital 'staining' technique. Lectin histochemistry revealed an almost complete abolition of specific lectin binding sites of affected endothelial cells. The findings indicate a significant deterioration by beta-amyloid (1-42) peptide of blood-brain barrier function and suggest that this may result from endothelial damage. It is assumed that altered permeability of cerebral vessels may be involved in the development of brain pathologies associated with Alzheimer's disease.