Defining CCL20’s Role in Carcinogenesis

It has become widely accepted that chronic inflammation is correlated with cancer. An important aspect in this relationship is the microenvironment established by inflammation and characterized by the production of small molecules known as cytokines and chemokines. One such chemokine, CCLZO, is a Th17 specific chemokine essential for Th17 activation. Although the contribution of Th1 and Th2 in carcinogenesis have been well established, Th17\u27s role in cancer development has yet to be identified. In this study, we provide first experimental evidence regarding the functional role of CCL20 in turmorigenesis that can shed light onto Th17\u27s function in cancer. We generated a tumor cell line with an inducible expression of CCLZO. An in vivo tumorigenesis study was carried out with the CCLZO inducible cell line and we found that when CCLZO was over expressed, it lead to a general trend of increased tumor size. It was also discovered that CCL20 expression is present throughout cancer development, but is most consistently expressed at the beginning stages of progression. CCL20 expression could produce a microenvironment that is favorable for tumor growth and Th17\u27s may function to support cancer progression

Soft-gluon Resummation for High-pT Inclusive-Hadron Production at COMPASS

We study the cross section for the photoproduction reaction gamma N -> h X in fixed-target scattering at COMPASS, where the hadron h is produced at large transverse momentum. We investigate the role played by higher-order QCD corrections to the cross section. In particular we address large logarithmic "threshold" corrections to the rapidity dependent partonic cross sections, which we resum to all orders at next-to-leading accuracy. In our comparison to the experimental data we find that the threshold contributions are large and improve the agreement between data and theoretical predictions significantly.Comment: 13 pages, 7 figures, journal versio

RACIAL AND ETHNIC DISPARITIES IN THE CRIMINAL JUSTICE SYSTEM IN NEBRASKA

What are racial and ethnic disparities (RED)? RED refers to racial and ethnic differences in contacts and experiences with the criminal and juvenile justice systems.1,2 Measuring the extent to which RED exist in the justice system is a first step toward identifying the ways to improve upon how well the system upholds the principle of equal treatment under the law.3 Prior research shows that RED are prevalent across multiple points of contact with the juvenile justice system in Nebraska.1,3 There is also a large body of evidence demonstrating RED in the adult criminal justice system nationwide.4 The purpose of this brief is to describe what the data show regarding racial disparities in the state of Nebraska and what is yet to be understood. Are there racial disparities in arrests in Nebraska? Relative to the racial makeup of the state population, there is significant disparity in the racial composition of the arrests in each year from 2014 to 2019.5,6 Inequity for African Americans is the largest contributor to the overall disparity. As shown in Figure 1, from 2014 to 2019, African Americans made up approximately 5% of the state population but accounted for 17.45–20.82% of arrests. American Indians/Alaskan Natives were also overrepresented in arrests (3.23–3.59%) relative to their portion the population (approximately 1%). Whites and Asians/Pacific Islanders are underrepresented in all six years

COVID-19 Impact on Nebraska Businesses: Nebraska Business Response Survey Report Round 1

The State of Nebraska, the Nebraska Chamber of Commerce, the University of Nebraska and several local project partners came together to develop and share the Nebraska Business Response Survey to understand the impact coronavirus (COVID-19) is having on the revenue and workforce of organizations across the state and find the best ways to support our business and nonprofit community during this crisis. The survey launched Wednesday, April 15, 2020, at 2 P.M. and closed Friday, April 24, 2020, at 5 P.M. The survey was only made available online and in English and Spanish. The survey was translated into Spanish by Lissette Aliaga-Linares, Ph.D., assistant professor of sociology and anthropology at the University of Nebraska at Omaha. The survey was distributed by email invitation from survey partners to their organization’s associates and publicly announced at a press conference by Pete Ricketts, Governor of the State of Nebraska. After the first 100 responses were received, a real-time, publicly available summary of each question response was made available at cpar.unomaha.edu\nebusinessresults. The summary report can still be accessed at that website. A series of reports using the survey data will be made available throughout May of 2020. This report provides an executive summary for the survey and analysis of quantitative survey questions by industry and by regions in Nebraska. The regions are based on zip codes in community college districts. An additional region was created in the area of the City of Lincoln due to the high number of responses. First, the survey results can only represent the views of those that responded during the 10 days that the survey was open. We recognize that the current global pandemic is rapidly evolving and thus viewpoints may evolve as well. Second, not all respondents answered all questions. Thus, the percentages and the number of respondents are given for most data points in the report and do vary across questions. Finally, in some places results may not add up to 100% due to rounding

Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis

Introduction: Type 4 phosphodiesterases (PDE4) play an important role in immune cells through the hydrolysis of the second messenger, cAMP. Inhibition of PDE4 has previously been shown to suppress immune and inflammatory responses, demonstrating PDE4 to be a valid therapeutic target for immune-mediated pathologies. We assessed the anti-inflammatory effects of a novel PDE4 inhibitor, apremilast, in human synovial cells from rheumatoid arthritis (RA) patients, as well as two murine models of arthritis

The Worksite Health Promotion Capacity Instrument (WHPCI): development, validation and approaches for determining companies' levels of health promotion capacity

<p>Abstract</p> <p>Background</p> <p>The Worksite Health Promotion Capacity Instrument (WHPCI) was developed to assess two key factors for effective worksite health promotion: collective willingness and the systematic implementation of health promotion activities in companies. This study evaluates the diagnostic qualities of the WHPCI based on its subscales Health Promotion Willingness and Health Promotion Management, which can be used to place companies into four different categories based on their level of health promotion capacity.</p> <p>Methods</p> <p>Psychometric evaluation was conducted using exploratory factor and reliability analyses with data taken from a random sample of managers from n = 522 German information and communication technology (ICT) companies. Receiver operating characteristic (ROC) analyses were conducted to determine further diagnostic qualities of the instrument and to establish the cut-off scores used to determine each company's level of health promotion capacity.</p> <p>Results</p> <p>The instrument's subscales, Health Promotion Willingness and Health Promotion Management, are based on one-dimensional constructs, each with very good reliability (Cronbach's alpha = 0.83/0.91). ROC analyses demonstrated satisfactory diagnostic accuracy with an area under the curve (AUC) of 0.76 (SE = 0.021; 95% CI 0.72-0.80) for the Health Promotion Willingness scale and 0.81 (SE = 0.021; 95% CI 0.77-0.86) for the Health Promotion Management scale. A cut-off score with good sensitivity (71%/76%) and specificity (69%/75%) was determined for each scale. Both scales were found to have good predictive power and exhibited good efficiency.</p> <p>Conclusions</p> <p>Our findings indicate preliminary evidence for the validity and reliability of both subscales of the WHPCI. The goodness of each cut-off score suggests that the scales are appropriate for determining companies' levels of health promotion capacity. Support in implementing (systematic) worksite health promotion can then be tailored to each company's needs based on their current capacity level.</p

Ena/VASP proteins have an anti-capping independent function in filopodia formation

Author Posting. © American Society for Cell Biology, 2007. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 18 (2007): 2579-2591, doi:10.1091/mbc.E06-11-0990.Filopodia have been implicated in a number of diverse cellular processes including growth-cone path finding, wound healing, and metastasis. The Ena/VASP family of proteins has emerged as key to filopodia formation but the exact mechanism for how they function has yet to be fully elucidated. Using cell spreading as a model system in combination with small interfering RNA depletion of Capping Protein, we determined that Ena/VASP proteins have a role beyond anticapping activity in filopodia formation. Analysis of mutant Ena/VASP proteins demonstrated that the entire EVH2 domain was the minimal domain required for filopodia formation. Fluorescent recovery after photobleaching data indicate that Ena/VASP proteins rapidly exchange at the leading edge of lamellipodia, whereas virtually no exchange occurred at filopodial tips. Mutation of the G-actin–binding motif (GAB) partially compromised stabilization of Ena/VASP at filopodia tips. These observations led us to propose a model where the EVH2 domain of Ena/VASP induces and maintains clustering of the barbed ends of actin filaments, which putatively corresponds to a transition from lamellipodial to filopodial localization. Furthermore, the EVH1 domain, together with the GAB motif in the EVH2 domain, helps to maintain Ena/VASP at the growing barbed ends.This work was supported in part by National Institutes of Health Grants GM7542201 to D.A.A., GM58801 to F.B.G., and GM62431 to G.G.B. and by Cell Migration Consortium Grants GM64346 to D.A.A and G.G.B

52 Genetic Loci Influencing Myocardial Mass.

BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets