Football: a counterpoint to the procession of pain on the Western Front, 1914-1918?

In this article, three artworks of the First World War containing images of recreational football are analysed. These three images, In the Wings of the Theatre of War, Artillery Men at Football and Gassed, span the war from its beginning to its conclusion and are discussed in relationship to the development of recreational football in the front-line area, the evolving policies of censorship and propaganda and in consideration of the national mood in Britain. The paper shows how football went from being a spontaneous and improvised pastime in the early stages of the war to a well organized entertainment by war’s end. The images demonstrate how the war was portrayed as a temporary affair by a confident nation in 1914 to a more resigned acceptance of a semi-permanent event to be endured by 1918; however, all three artworks show that the sporting spirit, and hence the fighting spirit, of the British soldier was intact

Detection of submicroscopic chromosomal abnormalities using microarray analysis:The value and pitfalls in prenatal and postnatal diagnosis

Chromosomal microarray enables identifying small genomic deletions and duplications that are not routinely seen on karyotyping. Microarray analysis therefore has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children in the Netherlands since 2008. When invasive prenatal diagnosis is indicated, because of ultrasound abnormalities and/or an increased risk for common aneuploidies (trisomy 21, 18 or 13) at first trimester screening, microarray analysis instead of conventional karyotyping will be applied when targeted molecular rapid aneuploidy detection reveals no abnormalities. Microarray analysis provides around 12-15% extra diagnosis in cases of mental retardation and/or structural abnormalities and it can provide 6% extra diagnosis in prenatal samples with a normal karyotype. Besides finding evident causative abnormalities, microarray analysis increases the detection rates of VOUS (variants of unknown significance) that, in particular during a pregnancy, induce emotional burden en counselling difficulties. Furthermore, CNVs that are pathogenic but not related with the phenotype (e.g. deletion of an oncogene) may complicate pretest and posttest counselling as well, since these findings may have health consequences for both patient and family members. Clinicians who request microarray analysis should be aware of these implications. In this paper, two prenatal and four postnatal case reports illustrate the ability to identify more clinically relevant abnormalities, but also limitations and coincidental findings in microarray analysis.</p

Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration

Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter the inflamed tissue. Evidence accumulates that leukocytes use preferred exit sites, alhough it is not yet clear how these hotspots in the endothelium are defined and how they are recognized by the leukocyte. Using lattice light sheet microscopy, we discovered that leukocytes prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, these junctional membrane protrusions are present in an asymmetric manner, meaning that one endothelial cell shows the protrusion and the adjacent one does not. Consequently, leukocytes cross the junction by migrating underneath the protruding endothelial cell. These protrusions depend on Rac1 activity and by using a photo-activatable Rac1 probe, we could artificially generate local exit-sites for leukocytes. Overall, we have discovered a new mechanism that uses local induced junctional membrane protrusions to facilitate/steer the leukocyte escape/exit from inflamed vessel walls

Assembly of the Pseudomonas aeruginosa type II secretion system

The Gram-negative bacterium Pseudomonas aeruginosa is the most common pathogen responsible for acute respiratory infections in immuno-compromised patients and for chronic infections in patients suffering from cystic fibrosis. Besides the high incidence and the severity of infections, increased resistance to conventional antibiotics forms a problem. Type II secretion largely contributes to the virulence of this bacterium. P. aeruginosa contains two secretion machineries of the type II kind, of which the Xcp system is responsible for the secretion of the majority of the exoproteins. The Xcp system is assembled from 12 constituents and five of these share N-terminal sequence similarity with the structural component of type IV pili, PilA, and are therefore designated pseudopilins. Type IV pilins and pseudopilins are found in various prokaryotic envelope protein complexes, including type IV pili and type II secretion machineries of Gram-negative bacteria, competence systems of Gram-positive bacteria, and flagella and sugar-binding structures within the archaeal kingdom. The precursors of these proteins have highly conserved N termini, consisting of a short positively charged leader peptide, which is cleaved off by a dedicated peptidase during maturation, and a hydrophobic stretch of approximately 20 amino acid residues. The presence of proteins with prepilin-like N termini always coincides with the occurrence of accessory proteins, including a prepilin peptidase, an ATPase and a multispanning transmembrane protein. Inner membrane translocation of pseudopilins has been suggested to depend on these accessory proteins. However, we show that the major pseudopilin of the Xcp system, XcpT, is co-translationally transported across the inner membrane via the SRP/Sec pathway. In support of a general translocation route for pilins and pseudopilins, we demonstrate that the hydrophobic N terminus of XcpT could be substituted by that of PilA without a loss of function. Furthermore, our data reveal that the accessory multispanning transmembrane protein, XcpS, participates in the inner membrane complex of the Xcp system. We show that simultaneous interaction with XcpR and XcpY increased the stability of the XcpS protein and that this interaction requires the large cytoplasmic loop of XcpS. Finally, we describe the reconstitution of the Xcp system in the heterologous hosts Pseudomonas putida and E. coli. These experiments show that targeting of the XcpQ protein to the outer membrane can be an important bottleneck in the reconstitution of the system in a heterologous host. These studies were performed to determine whether the known Xcp components are sufficient for their assembly into a functional machine. Together, the work described in this thesis gives more insight into the assembly of the P. aeruginosa Xcp machinery

Dail Eireann debate. Adjournment debate - controlled substances.

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