CXCR4 expression heterogeneity in neuroblastoma cells due to ligand-independent regulation

<p>Abstract</p> <p>Background</p> <p>CXCR4, the receptor for the chemokine stromal-derived factor 1 (SDF-1), has been shown to mediate many of the processes essential for cancer progression such as tumor cell proliferation, metastasis, and angiogenesis. To understand the role of CXCR4 in the biology of neuroblastoma, a disease that presents with wide spread metastases in over 50% of patients, we screened ten patient derived-neuroblastoma cell-lines for basal CXCR4 expression and sought to identify characteristics that correlate with tumor cell phenotype.</p> <p>Results</p> <p>All cell lines expressed <it>CXCR4 </it>mRNA at variable levels, that correlated well with three distinct classes of CXCR4 surface expression (low, moderate, or high) as defined by flow cytometry. Analysis of the kinetics of CXCR4 surface expression on moderate and high expressing cell lines showed a time-dependent down-regulation of the receptor that directly correlated with cell confluency, and was independent of SDF1. Cell lysates showed the presence of multiple CXCR4 isoforms with three major species of approximately 87, 67 and 55 kDa associating with high surface expression, and two distinct species of 45 and 38 kDa correlating with low to null surface expression. Western blot analysis of CXCR4 immunoprecipitates showed that the 87 and 67 kDa forms were ubiquitinated, while the others were not. Finally, treatment of cells with a proteasome inhibitor resulted in down regulation of CXCR4 surface expression.</p> <p>Conclusions</p> <p>Taken together, these data show that regulation of CXCR4 surface expression in neuroblastoma cells can occur independently of SDF-1 contribution arguing against an autocrine mechanism. Additionally these data suggest that post-translational modifications of CXCR4, in part through direct ubiquitination, can influence trafficking of CXCR4 to the surface of neuroblastoma cells in a ligand-independent manner.</p

Thermomechanical Stability of Ultrananocrystalline Diamond

We have measured mechanical stiffness and dissipation in ultrananocrystalline diamond (UNCD) from 63 K to 450 K using microcantilever resonators in a custom ultrahigh vacuum (UHV) atomic force microscope. UNCD exhibits a temperature coefficient of modulus that is found to be extremely low: -26 ppm/K, which is close to the previously measured value of -24 ppm/K for single crystal diamond. The magnitude and the temperature dependence of dissipation are consistent with the behavior of disordered systems. The results indicate that defects, most likely at the grain boundaries, create the dominant contribution to mechanical dissipation. These measurements of modulus and dissipation versus temperature in this temperature range in UNCD establish the nanostructure’s effect on the thermomechanical stability and suggest routes for tailoring these properties

Assessing direct contributions of morphological awareness and prosodic sensitivity to children’s word reading and reading comprehension

We examined the independent contributions of prosodic sensitivity and morphological awareness to word reading, text reading accuracy, and reading comprehension. We did so in a longitudinal study of English-speaking children (N = 70). At 5 to 7 years of age, children completed the metalinguistic measures along with control measures of phonological awareness and vocabulary. Children completed the reading measures two years later. Morphological awareness, but not prosodic sensitivity made a significant independent contribution to word reading, text reading accuracy and reading comprehension. The effects of morphological awareness on reading comprehension remained after controls for word reading. These results suggest that morphological awareness needs to be considered seriously in models of reading development and that prosodic sensitivity might have primarily indirect relations to reading outcomes. Keywords: Morphological Awareness; Prosody; Word Reading; Reading Comprehension

The development of a program analysis environment for Ada

A unit level, Ada software module testing system, called Query Utility Environment for Software Testing of Ada (QUEST/Ada), is described. The project calls for the design and development of a prototype system. QUEST/Ada design began with a definition of the overall system structure and a description of component dependencies. The project team was divided into three groups to resolve the preliminary designs of the parser/scanner: the test data generator, and the test coverage analyzer. The Phase 1 report is a working document from which the system documentation will evolve. It provides history, a guide to report sections, a literature review, the definition of the system structure and high level interfaces, descriptions of the prototype scope, the three major components, and the plan for the remainder of the project. The appendices include specifications, statistics, two papers derived from the current research, a preliminary users' manual, and the proposal and work plan for Phase 2

ROCs in Eyewitness Identification:Instructions versus Confidence Ratings

From the perspective of signal-detection theory, different lineup instructions may induce different levels of response bias (Clark, 2005). If so, then collecting correct and false identification rates across different instructional conditions will trace out the ROC – the same ROC that, theoretically, could also be traced out from a single instruction condition in which each eyewitness decision is accompanied by a confidence rating. We tested whether the two approaches do in fact yield the same ROC. Participants were assigned to a confidence rating condition or to an instructional biasing condition (liberal, neutral, unbiased, or conservative). After watching a video of a mock crime, participants were presented with instructions followed by a 6-person simultaneous photo lineup. The ROCs from both methods were similar, but they were not exactly the same. These findings have potentially important policy implications for how the legal system should go about controlling eyewitness response bias

ROCs in Eyewitness Identification: Instructions vs. Confidence Ratings

From the perspective of signal-detection theory, different lineup instructions may induce different levels of response bias (Clark, 2005). If so, then collecting correct and false identification rates across different instructional conditions will trace out the ROC – the same ROC that, theoretically, could also be traced out from a single instruction condition in which each eyewitness decision is accompanied by a confidence rating. We tested whether the two approaches do in fact yield the same ROC. Participants were assigned to a confidence rating condition or to an instructional biasing condition (liberal, neutral, unbiased, or conservative). After watching a video of a mock crime, participants were presented with instructions followed by a 6-person simultaneous photo lineup. The ROCs from both methods were similar, but they were not exactly the same. These findings have potentially important policy implications for how the legal system should go about controlling eyewitness response bias

Social identity and acceptability of wild pig (Sus scrofa) control actions: A case study of Texas hunters

Wild pigs (Sus scrofa) pose significant challenges to wildlife managers. This research explored Texas hunters’ acceptability of wild pig control actions, and whether acceptability varied according to hunters’ affiliation with four different categories of natural resource organizations as an indicator of social identity. Results of a survey (n = 37,317) revealed that most hunters were accepting of all control actions except toxicants and non-lethal deterrents. Mean acceptability scores for each action differed significantly across the four affiliation categories, but effect sizes were minimal. Hunters affiliated with agricultural organizations were the most accepting of control actions, while hunters with no organizational affiliations were least accepting. Findings suggested that while the type of organization with which a hunter affiliates provides some basis for predicting acceptability of control actions, the association is likely not significant enough to warrant differentiating wild pig outreach messaging on the basis of affiliation

Texas Hunters’ Perceptions Regarding the Acceptability of Toxicants to Control Wild Pig Populations

Wild pigs (Sus scrofa) are an invasive species in the United States. They damage agriculture, degrade water quality and ecological communities, and host a number of viruses, parasites, and bacteria transmissible to humans and animals. In states such as Texas, USA, where wild pigs cause extensive damage to agriculture and property, officials have considered allowing for the use of toxicants to control wild pig populations. To provide decision-makers with information regarding stakeholders’ perceptions of the use of toxicants to control wild pigs, we surveyed Texas hunters in 2019 to assess the level of acceptance of a hypothetical wild pig toxicant, the sociodemographic and other factors most closely associated with acceptability of such a toxicant, and the specific concerns that underlie hunters’ positions on the use of such a toxicant. We received 37,317 completed responses to an online, self-administered survey. Respondents were divided over the use of a toxicant, with 43% finding a toxicant acceptable, 18% neutral, and 39% finding a toxicant unacceptable. The factor most closely associated with acceptance of a wild pig toxicant was respondents’ desired wild pig population size in Texas (χ2 = 3,657.7, P \u3c 0.001, V = 0.26), with 70% of respondents who preferred that wild pigs be completely removed from Texas finding the use of a toxicant to be acceptable, compared to 14% of respondents who preferred that wild pig populations increase or stay the same. The most commonly raised concerns in connection with toxicant usage were potential negative impacts to nontarget animals (33%) and negative impacts to human health (24%). Our research suggests that while achieving a consensus among Texas hunters on toxicant usage is unrealistic, building majority support may be possible if the identified concerns are sufficiently addressed in product development and outreach