Scatter factor : molecular characteristics and effect on the invasiveness of epithelial cells

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We have previously shown that MDCK epithelial cells, which are deprived of intracellular adhesion by the addition of anti-Arc-1/uvomorulin antibodies, become invasive for collagen gels and embryonal heart tissue (Behrens, J., M. M. Mareel, F. M. Van Roy, and W. Birchmeier. 1989. J. Cell Biol. 108: 2435-2447.). Here we examined whether invasiveness is also induced by scatter factor, which is known to dissociate epithelial cells (Stoker, M., E. Gherardi, M. Perryman, and J. Gray. 1987. Nature (Lond.). 327:239-242.). Scatter factor was purified to homogeneity from conditioned medium of human fibroblasts by heparin-Sepharose chromatography, followed by cation exchange chromatography, gel filtration, or preparative SDS gel electrophoresis. We found that scatter factor represents a 92,000 mol wt glycoprotein which, apparently, is converted by limited proteolysis into disulfide-linked 62,000 and 34/32,000 mol wt subunits. Reversed phase HPLC and sequence analysis of tryptic peptides confirmed the suggested molecular structure, and revealed further that scatter factor exhibits sequence similarities to hepatocyte growth factor and to plasminogen. Purified scatter factor in fact induces the invasiveness into collagen matrices of MDCK epithelial cells, and induces or promotes the invasiveness of a number of human carcinoma cell lines. Apparently, the effect on the human cells depends on their respective degree of differentiation, i.e., cell lines with a less pronounced epithelial phenotype were more susceptible to the factor. Scatter factor does not seem to influence synthesis, steady-state level, and phosphorylation of the cell adhesion molecule Arc-1/uvomorulin. Thus, scatter factor represents a clearly defined molecular species which induces, in vitro, the progression of epithelial cells to a more motile, i.e., invasive phenotype

Michigan Publishing Backlist Rights and Permissions Project

This poster was originally presented at the 2015 Library Publishing Forum in Portland, Oregon.In 2013, Michigan Publishing undertook a Rights and Permissions Project to evaluate the rights of, and effect use cases for, all of its digitized backlist titles; nearly 4,000 titles had been digitized in a previous phase of the project. As of March 2015, this project has assessed the rights of over 2,000 of those backlist titles. This poster gives an overview of the workflow involved in assessing the rights for each title, and the considerations for bringing suitable titles back into circulation.http://deepblue.lib.umich.edu/bitstream/2027.42/110947/1/Birchmeier_LPC-Forum_2015.pdf17Description of Birchmeier_LPC-Forum_2015.pdf : Project Update Poste

Bayesian estimation of (co) variance components in Argentinian Brangus for carcass traits using the FCG algorithm

Se emplearon los datos de 2273 toritos y vaquillonas Brangus para estimar las heredabilidades (h2 ) y las correlaciones aditivas y ambientales de caracteres de calidad de carne medidos por ultrasonido. Los registros provenían del programa de evaluación genética de la Asociación Argentina de Brangus. Los caracteres medidos fueron el área del ojo del bife (AOB), el marmoreado (MB), la grasa dorsal (GD) y la grasa de cadera (GC). La edad media de los animales al momento de la medición fue 641 días en machos y 685 días en hembras. Los parámetros genéticos y ambientales fueron estimados mediante un algoritmo bayesiano conjugado. Los valores estimados de h2 fueron 0,22, 0,16, 0,12 y 0,21, para AOB, GD, CC y MB, respectivamente. En términos generales, las estimaciones de las correlaciones genéticas y ambientales se encontraron cercanas a la cifra media de la literatura. Si bien los valores estimados de h2 fueron inferiores al promedio de la investigación realizada en vacunos para carne, la variabilidad encontrada es suficiente como para que la respuesta a la selección por estos caracteres – empleando predicciones de los valores de cría calculadas con los parámetros estimados - sea moderadamente efectiva.Data on 2273 Brangus young bulls and heifers were used to estimate heritabilities (h2 ) and genetics and environmental correlations for ultrasound carcass measures. Records were from the genetic evaluation program of Asociación Argentina de Brangus. Traits measured were rib-eye area (AOB), marbling (MB), back-fat thickness (GD), and hip-fat thickness (GC). Average ages of measure were 641 days in males and 685 in females. The genetic and environmental dispersion parameters were estimated by a conjugate Bayesian algorithm (FCG). Estimates of h2 were 0,22, 0,16, 0,12, and 0,21, for AOB, GD, CC, and MB, respectively. In general, estimates of genetic and environmental correlations were close to the average published values. Even tough estimates of h2 were below the average of published estimates for beef cattle, the additive genetic variation found in the current study would lead to a moderate response to selection – using predictions of breeding value that are calculated with the estimate parameters.Fil: Cantet, Rodolfo Juan Carlos. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Birchmeier, A. N.. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentin

Expression and rearrangement of the ROS1 gene in human glioblastoma cells

The human ROS1 gene, which possibly encodes a growth factor receptor, was found to be expressed in human tumor cell lines. In a survey of 45 different human cell lines, we found ROS1 to be expressed in glioblastoma-derived cell lines at high levels and not to be expressed at all, or expressed at very low levels, in the remaining cell lines. The ROS1 gene was present in normal copy numbers in all cell lines that expressed the gene. However, in one particular glioblastoma line, we detected a potentially activating mutation at the ROS1 locus

Parallelism and divergence in immune responses: a comparison of expression levels in two lakes

Question: How do immune phenotypes differ between infected and uninfected wild individuals, and is the effect the same in different populations? Organisms: Threespine stickleback (Gasterosteus aculeatus) from two lake populations on the island of North Uist, Scotland, sampled in May 2015. Methods: For each fish, we recorded length, sex, reproductive status, condition, and parasitic infection. We measured the expression levels of eight genes that act as key markers of immune system function using qPCR, and then examined the relationship between measured factors and immune gene expression profiles within each population. Conclusions: Populations differed significantly in their immune gene expression profiles. Within each population, multiple factors, including condition, reproductive status, and Schistocephalus solidus infection levels, were found to correlate with expression levels of different arms of the immune system

Findings from Year Two of the External Evaluation of the Healthy & Active Communities Initiative

The Missouri Foundation for Health has funded 33 projects under its Healthy & Active Communities (H&AC) Initiative in two-year funding cycles. A set of 15 projects was funded beginning in 2005 while a set of 18 was funded starting in 2006. This report is the second of three annual reports that assess the extent to which the H&AC Initiative is achieving its objectives. The report builds upon the findings described in “Findings from Year One of the External Evaluation of the Healthy & Active Communities Initiative.” The Missouri Foundation for Health contracted with the Institute of Public Policy, Truman School of Public Affairs at the University of Missouri to provide an evaluation of the success of the Initiative as a whole. This focus differs from the typical evaluation where evaluators are assessing and reporting on the success of individual funded projects. Instead, the evaluation looked across the funded projects to identify common factors of success. Continuing from the framework established in 2006, the evaluation team worked from a socio-ecological model. This model assumes that complex prevention programs such as the H&AC projects must use a multi-faceted approach in order to change behavior on individual, organizational and community levels simultaneously. To evaluate programs with multiple approaches such as these, the evaluators determined that cluster evaluation, a strategy developed by the Kellogg Foundation, could be used to identify successful features of the Initiative as a whole. This method enables the evaluators to identify successful program and community conditions that transcend the individual projects

Pericellular activation of hepatocyte growth factor by the transmembrane serine proteases matriptase and hepsin, but not by the membrane-associated protease uPA

HGF (hepatocyte growth factor) is a pleiotropic cytokine homologous to the serine protease zymogen plasminogen that requires canonical proteolytic cleavage to gain functional activity. The activating proteases are key components of its regulation, but controversy surrounds their identity. Using quantitative analysis we found no evidence for activation by uPA (urokinase plasminogen activator), despite reports that this is a principal activator of pro-HGF. This was unaffected by a wide range of experimental conditions, including the use of various molecular forms of both HGF and uPA, and the presence of uPAR (uPA receptor) or heparin. In contrast the catalytic domains of the TTSPs (type-II transmembrane serine proteases) matriptase and hepsin were highly efficient activators (50% activation at 0.1 and 3.4 nM respectively), at least four orders of magnitude more efficient than uPA. PS-SCL (positional-scanning synthetic combinatorial peptide libraries) were used to identify consensus sequences for the TTSPs, which in the case of hepsin corresponded to the pro-HGF activation sequence, demonstrating a high specificity for this reaction. Both TTSPs were also found to be efficient activators at the cell surface. Activation of pro-HGF by PC3 prostate carcinoma cells was abolished by both protease inhibition and matriptase-targeting siRNA (small interfering RNA), and scattering of MDCK (Madin–Darby canine kidney) cells in the presence of pro-HGF was abolished by inhibition of matriptase. Hepsin-transfected HEK (human embryonic kidney)-293 cells also activated pro-HGF. These observations demonstrate that, in contrast with the uPA/uPAR system, the TTSPs matriptase and hepsin are direct pericellular activators of pro-HGF, and that together these proteins may form a pathway contributing to their involvement in pathological situations, including cancer

Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo.

In chronic infection and cancer, T cells acquire a dysfunctional state characterized by the expression of inhibitory receptors. In vitro studies implicated the phosphatase Shp-2 downstream of these receptors, including PD-1. However, whether Shp-2 is responsible in vivo for such dysfunctional responses remains elusive. To address this, we generated T cell-specific Shp-2-deficient mice. These mice did not show differences in controlling chronic viral infections. In this context, Shp-2-deleted CD8 <sup>+</sup> T lymphocytes expanded moderately better but were less polyfunctional than control cells. Mice with Shp-2-deficient T cells also showed no significant improvement in controlling immunogenic tumors and responded similarly to controls to α-PD-1 treatment. We therefore showed that Shp-2 is dispensable in T cells for globally establishing exhaustion and for PD-1 signaling in vivo. These results reveal the existence of redundant mechanisms downstream of inhibitory receptors and represent the foundation for defining these relevant molecular events

Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development

The ErbB2 tyrosine kinase functions as coreceptor for the neuregulin receptors ErbB3 and ErbB4 and can participate in signaling of EGF receptor (ErbB1), interleukin receptor gp130, and G-protein coupled receptors. ErbB2−/− mice die at midgestation because of heart malformation. Here, we report a genetic rescue of their heart development by myocardial expression of erbB2 cDNA that allows survival of the mutants to birth. In rescued erbB2 mutants, Schwann cells are lacking. Motoneurons form and can project to muscle, but nerves are poorly fasciculated and disorganized. Neuromuscular junctions form, as reflected in clustering of AChR and postsynaptic expression of the genes encoding the a-AChR, AChE, e-AChR, and the RI subunit of the cAMP protein kinase. However, a severe loss of motoneurons on cervical and lumbar, but not on thoracic levels occurs. Our results define the roles of Schwann cells during motoneuron and synapse development, and reveal different survival requirements for distinct motoneuron population

Does Installing Artificial Turf Create a Honeymoon Effect for College Football Teams?

Most research conducted related to the honeymoon effect and attendance focused on Major League Baseball and stadium renovation. This study however, examined the connection between attendance and installation of artificial turf at the collegiate level. Seven Division I Football Bowl Subdivision Universities in Ohio have installed artificial turf and hosted home games for at least four full seasons. Cincinnati and Miami (Ohio) fit the honeymoon theory, reaching maximum attendance numbers in year two and leveling out by year four