Natural CD4+ T-Cell Responses against Indoleamine 2,3-Dioxygenase

The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.In the present study, we show that CD4(+) helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4(+) T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4(+) T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4(+) T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4(+) T cells and CD8(+) CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4(+) T cells.IDO is spontaneously recognized by HLA class II-restricted, CD4(+) T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4(+) responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression

On a Clique-Based Integer Programming Formulation of Vertex Colouring with Applications in Course Timetabling

Vertex colouring is a well-known problem in combinatorial optimisation, whose alternative integer programming formulations have recently attracted considerable attention. This paper briefly surveys seven known formulations of vertex colouring and introduces a formulation of vertex colouring using a suitable clique partition of the graph. This formulation is applicable in timetabling applications, where such a clique partition of the conflict graph is given implicitly. In contrast with some alternatives, the presented formulation can also be easily extended to accommodate complex performance indicators (``soft constraints'') imposed in a number of real-life course timetabling applications. Its performance depends on the quality of the clique partition, but encouraging empirical results for the Udine Course Timetabling problem are reported

A critical appraisal of appendage disparity and homology in fishes

Fishes are both extremely diverse and morphologically disparate. Part of this disparity can be observed in the numerous possible fin configurations that may differ in terms of the number of fins as well as fin shapes, sizes and relative positions on the body. Here, we thoroughly review the major patterns of disparity in fin configurations for each major group of fishes and discuss how median and paired fin homologies have been interpreted over time. When taking into account the entire span of fish diversity, including both extant and fossil taxa, the disparity in fin morphologies greatly complicates inferring homologies for individual fins. Given the phylogenetic scope of this review, structural and topological criteria appear to be the most useful indicators of fin identity. We further suggest that it may be advantageous to consider some of these fin homologies as nested within the larger framework of homologous fin‐forming morphogenetic fields. We also discuss scenarios of appendage evolution and suggest that modularity may have played a key role in appendage disparification. Fin modules re‐expressed within the boundaries of fin‐forming fields could explain how some fins may have evolved numerous times independently in separate lineages (e.g., adipose fin), or how new fins may have evolved over time (e.g., anterior and posterior dorsal fins, pectoral and pelvic fins). We favour an evolutionary scenario whereby median appendages appeared from a unique field of competence first positioned throughout the dorsal and ventral midlines, which was then redeployed laterally leading to paired appendages.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151971/1/faf12402_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151971/2/faf12402.pd

Osteochondral defects in the ankle: why painful?

Osteochondral defects of the ankle can either heal and remain asymptomatic or progress to deep ankle pain on weight bearing and formation of subchondral bone cysts. The development of a symptomatic OD depends on various factors, including the damage and insufficient repair of the subchondral bone plate. The ankle joint has a high congruency. During loading, compressed cartilage forces its water into the microfractured subchondral bone, leading to a localized high increased flow and pressure of fluid in the subchondral bone. This will result in local osteolysis and can explain the slow development of a subchondral cyst. The pain does not arise from the cartilage lesion, but is most probably caused by repetitive high fluid pressure during walking, which results in stimulation of the highly innervated subchondral bone underneath the cartilage defect. Understanding the natural history of osteochondral defects could lead to the development of strategies for preventing progressive joint damage

Chondromatous Hamartoma of the Lung

Chondromatous hamartoma of the lung is a pulmonary "tumour " which, as a result of the progress made in thoracic surgery during the last decade, is now being reported as not particularly uncommon. Since a lack of familiarity with this tumour may give rise to clinical as well as to pathological errors, it seems justified to describe it in some detail. At the same time we will report our experience based on nine cases. The term hamartoma (&uocp'r&uet =to fail or to err) was first used in 1904 by the German pathologist Albrecht, who defined it as a tumour-like malformation of an organ, made up of the normal elements of that organ, but with abnormal mixing and quantity of the components and perhaps an abnormal degree of differen-tiation. The hamartomata originally described by Albrecht were cavernomata of the liver, cavernomata of the spleen, and tuberous fibromata of the medullary sub-stance of the kidney. Goldsworthy (1934) and Jaeger (1934) were the first to realize that the previously reported " chondromata " of the lung were not pure chondromata, but that they should be classified as hamartomas. The word " chondromatous&quot