University of Nebraska Omaha

About: University of Nebraska Omaha is a education organization based out in Omaha, Nebraska, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 4526 authors who have published 8905 publications receiving 213914 citations. The organization is also known as: UNO & University of Omaha.

3D Bioprinting of Breast Cancer Models for Drug Resistance Study

Abstract: Adipose-derived mesenchymal stem/stromal cells (ADMSC) are one of the major stromal cells in the breast cancer microenvironment that promote cancer progression. Previous studies on the effects of ADMSC on breast cancer metastasis and drug resistance, using two-dimensional (2D) cultures, remained inconclusive. In the present study, we compared cocultured ADMSC and human epidermal receptor 2 positive breast primary breast cancer cells (21PT) in 2D and three-dimensional (3D) cultures and then examined their response to doxorubicin (DOX). We examined 3D bioprinted constructs with breast cancer cells in the middle and ADMSC in the edge region, which were made by using dual hydrogel-based bioinks. We found that the percentage of cleaved Caspase-3 positive cells was significantly lower in the bioprinted constructs with ADMSC and 21PT than that in the cancer cell alone constructs, in response to low DOX dose. We further increased the thickness of the ADMSC layers to mimic the status of obesity and then examined the effect of ADMSC thickness on DOX resistance and lysyl oxidase (LOX) secretion. In the moderate and thick-layered ADMSC constructs, significantly more cells were stained negative for cleaved Caspase-3, indicating less apoptosis. Both ADMSC and 21PT intrinsically expressed LOX, regardless of changes in thickness or DOX administration. Notably, treatment with a LOX inhibitor significantly decreased the stiffness in the ADMSC region but did not affect the stiffness in the 21PT region. In addition, LOX inhibitor treatment enhanced DOX sensitivity of 21PT in the bioprinted constructs, as seen by a decrease in LOX secretion and downregulation of adenosine triphosphate-binding cassette transporter gene expression. Taken together, we demonstrate that 3D bioprinted these breast cancer models faithfully reproduce in vivo conditions and should provide better models for examining breast cancer biology and for screening for drug discoveries.

Sumoylation activates the transcriptional activity of Pax-6, an important transcription factor for eye and brain development

Abstract: Pax-6 is an evolutionarily conserved transcription factor regulating brain and eye development. Four Pax-6 isoforms have been reported previously. Although the longer Pax-6 isoforms (p46 and p48) bear two DNA-binding domains, the paired domain (PD) and the homeodomain (HD), the shorter Pax-6 isoform p32 contains only the HD for DNA binding. Although a third domain, the proline-, serine- and threonine-enriched activation (PST) domain, in the C termini of all Pax-6 isoforms mediates their transcriptional modulation via phosphorylation, how p32 Pax-6 could regulate target genes remains to be elucidated. In the present study, we show that sumoylation at K91 is required for p32 Pax-6 to bind to a HD-specific site and regulate expression of target genes. First, in vitro-synthesized p32 Pax-6 alone cannot bind the P3 sequence, which contains the HD recognition site, unless it is preincubated with nuclear extracts precleared by anti–Pax-6 but not by anti-small ubiquitin-related modifier 1 (anti-SUMO1) antibody. Second, in vitro-synthesized p32 Pax-6 can be sumoylated by SUMO1, and the sumoylated p32 Pax-6 then can bind to the P3 sequence. Third, Pax-6 and SUMO1 are colocalized in the embryonic optic and lens vesicles and can be coimmunoprecipitated. Finally, SUMO1-conjugated p32 Pax-6 exists in both the nucleus and cytoplasm, and sumoylation significantly enhances the DNA-binding ability of p32 Pax-6 and positively regulates gene expression. Together, our results demonstrate that sumoylation activates p32 Pax-6 in both DNA-binding and transcriptional activities. In addition, our studies demonstrate that p32 and p46 Pax-6 possess differential DNA-binding and regulatory activities.

A tale of two counties: Unemployment and sentence severity

Abstract: This study explores the relationship between the offender's employment status and sentence severity. We use data on felony offenders sentenced in 1993 in Chicago and in Kansas City to test a number of hypotheses concerning the effect of unemployment on the likelihood of incarceration and the length of the prison sentence. Our analyses reveal a complex relationship between unemployment and sentence severity: Unemployment had a direct effect on the decision to incarcerate or not only in Kansas City, and directly affected sentence length only in Chicago. In addition, unemployment interacted with other offender characteristics. The offender's employment status had no effect on either measure of sentence severity in either jurisdiction if the offender was white. In Chicago, unemployment increased the odds of incarceration for young males and for young Hispanic males, and increased the length of the sentence for males, young males, and black males. In Kansas City, unemployment had no effect on sentence length f...

Searching for a Role for Citizens in the Budget Process

Abstract: Citizen participation in the local budget process is not prevalent, despite encouragement from scholars and professional organizations. This case study of two Kansas cities that have used a variety of input mechanisms in the budget process analyzes the effectiveness of citizen budget participation. Limited effectiveness was found, which may largely be due to the timing of the input, unstated or unclear goals, implementation difficulties, and political and environmental constraints. Citizen input appears to have had little effect on budget decisions, and neither city has institutionalized participation in the process. However, the input mechanisms serve other purposes, such as education and support for specific proposals. Describing the benefits as well as the difficulty of involving citizens in a meaningful way is beneficial to other governments as they wrestle with the issue of defining the citizens' role in the budget process.