Friday Facts, December 6, 2013, Vol. 194

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

CD3 delta establishes a functional link between the T cell receptor and CD8.

T cells expressing T cell receptor (TCR) complexes that lack CD3 delta, either due to deletion of the CD3 delta gene, or by replacement of the connecting peptide of the TCR alpha chain, exhibit severely impaired positive selection and TCR-mediated activation of CD8 single-positive T cells. Because the same defects have been observed in mice expressing no CD8 beta or tailless CD8 beta, we examined whether CD3 delta serves to couple TCR.CD3 with CD8. To this end we used T cell hybridomas and transgenic mice expressing the T1 TCR, which recognizes a photoreactive derivative of the PbCS 252-260 peptide in the context of H-2K(d). We report that, in thymocytes and hybridomas expressing the T1 TCR.CD3 complex, CD8 alpha beta associates with the TCR. This association was not observed on T1 hybridomas expressing only CD8 alpha alpha or a CD3 delta(-) variant of the T1 TCR. CD3 delta was selectively co-immunoprecipitated with anti-CD8 antibodies, indicating an avid association of CD8 with CD3 delta. Because CD8 alpha beta is a raft constituent, due to this association a fraction of TCR.CD3 is raft-associated. Cross-linking of these TCR-CD8 adducts results in extensive TCR aggregate formation and intracellular calcium mobilization. Thus, CD3 delta couples TCR.CD3 with raft-associated CD8, which is required for effective activation and positive selection of CD8(+) T cells.

Friday Facts, December 13, 2013, Vol. 195

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Soluble major histocompatibility complex-peptide octamers with impaired CD8 binding selectively induce Fas-dependent apoptosis.

Fluorescence-labeled soluble major histocompatibility complex class I-peptide "tetramers" constitute a powerful tool to detect and isolate antigen-specific CD8(+) T cells by flow cytometry. Conventional "tetramers" are prepared by refolding of heavy and light chains with a specific peptide, enzymatic biotinylation at an added C-terminal biotinylation sequence, and "tetramerization" by reaction with phycoerythrin- or allophycocyanin-labeled avidin derivatives. We show here that such preparations are heterogeneous and describe a new procedure that allows the preparation of homogeneous tetra- or octameric major histocompatibility complex-peptide complexes. These compounds were tested on T1 cytotoxic T lymphocytes (CTLs), which recognize the Plasmodium berghei circumsporzoite peptide 252-260 (SYIPSAEKI) containing photoreactive 4-azidobenzoic acid on Lys(259) in the context of H-2K(d). We report that mutation of the CD8 binding site of K(d) greatly impairs the binding of tetrameric but not octameric or multimeric K(d)-PbCS(ABA) complexes to CTLs. This mutation abolishes the ability of the octamer to elicit significant phosphorylation of CD3, intracellular calcium mobilization, and CTL degranulation. Remarkably, however, this octamer efficiently activates CTLs for Fas (CD95)-dependent apoptosis.

Kansalaistuva politiikka? Huomioita kuntalaisaktiivisuudesta poliittisena toimijuutena

Abstract: Towards citizen politics? Notes on local resident actvism as political subjectivity

Friday Facts, December 20, 2013, Vol. 196

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, January 3, 2014, Vol. 197

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

The Iowa State Capitol Fire 1904, November 2012

The twenty-first century Iowa State Capitol contains state-of-the-art fire protection. Sprinklers and smoke detectors are located in every room and all public hallways are equipped with nearby hydrants. The Des Moines Fire Department is able to fight fires at nearly any height. However, on Monday morning, January 4, 1904, the circumstances were much different. By the beginning of 1904, the Capitol Improvement Commission had been working in the Capitol for about two years. The commissioners were in charge of decorating the public areas of the building, installing the artwork in the public areas, installing a new copper roof, re-gilding the dome, replacing windows, and connecting electrical lines throughout. Electrician H. Frazer had been working that morning in Committee Room Number Five behind the House Chamber, drilling into the walls to run electrical wires and using a candle to light his way. The investigating committee determined that Frazer had left his work area and had neglected to extinguish his candle. The initial fire alarm sounded at approximately 10 a.m. Many citizen volunteers came to help the fire department. Capitol employees and state officials also assisted in fighting the fire, including Governor Albert Cummins. The fire was finally brought under control around 6 p.m., although some newspaper accounts at the time reported that the fire continued smoldering for several days. Crampton Linley was the engineer working with the Capitol Improvement Commission. He was in the building at the time of the fire and was credited with saving the building. Linley crawled through attic areas to close doors separating wings of the Capitol, an action which smothered the flames and brought the fire under control. Sadly, Linley did not live long enough to be recognized for his heroism. The day after the fire, while examining the damage, Linley fell through the ceiling of the House Chamber and died instantly from severe head injuries. The flames had burned through the ceiling and caused much of it to collapse to the floor below, while the lower areas of the building had been damaged by smoke and water. Elmer Garnsey was the artist hired by the Capitol Improvement Commission to decorate the public areas of the building. Therefore, he seemed the logical candidate to be given the additional responsibility of redecorating the areas damaged by the fire. Garnsey had a very different vision for the decoration, which is why the House Chamber, the old Supreme Court Room, and the old Agriculture offices directly below the House Chamber have a design that is very different from the areas of the building untouched by the fire.

Friday Facts, January 10, 2014, Vol. 198

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, January 17, 2014, Vol. 199

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, January 31, 2014, Vol. 201

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, February 14, 2014, Vol. 202

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Inhibition of the Kit Ligand/c-Kit Axis Attenuates Metastasis in a Mouse Model Mimicking Local Breast Cancer Relapse after Radiotherapy.

PURPOSE: Local breast cancer relapse after breast-saving surgery and radiotherapy is associated with increased risk of distant metastasis formation. The mechanisms involved remain largely elusive. We used the well-characterized 4T1 syngeneic, orthotopic breast cancer model to identify novel mechanisms of postradiation metastasis. EXPERIMENTAL DESIGN: 4T1 cells were injected in 20 Gy preirradiated mammary tissue to mimic postradiation relapses, or in nonirradiated mammary tissue, as control, of immunocompetent BALB/c mice. Molecular, biochemical, cellular, histologic analyses, adoptive cell transfer, genetic, and pharmacologic interventions were carried out. RESULTS: Tumors growing in preirradiated mammary tissue had reduced angiogenesis and were more hypoxic, invasive, and metastatic to lung and lymph nodes compared with control tumors. Increased metastasis involved the mobilization of CD11b(+)c-Kit(+)Ly6G(high)Ly6C(low)(Gr1(+)) myeloid cells through the HIF1-dependent expression of Kit ligand (KitL) by hypoxic tumor cells. KitL-mobilized myeloid cells homed to primary tumors and premetastatic lungs, to give rise to CD11b(+)c-Kit(-) cells. Pharmacologic inhibition of HIF1, silencing of KitL expression in tumor cells, and inhibition of c-Kit with an anti-c-Kit-blocking antibody or with a tyrosine kinase inhibitor prevented the mobilization of CD11b(+)c-Kit(+) cells and attenuated metastasis. C-Kit inhibition was also effective in reducing mobilization of CD11b(+)c-Kit(+) cells and inhibiting lung metastasis after irradiation of established tumors. CONCLUSIONS: Our work defines KitL/c-Kit as a previously unidentified axis critically involved in promoting metastasis of 4T1 tumors growing in preirradiated mammary tissue. Pharmacologic inhibition of this axis represents a potential therapeutic strategy to prevent metastasis in breast cancer patients with local relapses after radiotherapy. Clin Cancer Res; 18(16); 4365-74. ©2012 AACR.

Friday Facts, February 28, 2014, Vol. 203

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

Friday Facts, March 7, 2014, Vol. 204

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.