Studies in Expressive Movement

Cover and several pages from Studies in Expressive Movement, a book about personality traits.https://dune.une.edu/scribesscrawlers/1000/thumbnail.jp

BID mediates selective killing of APC-deficient cells in intestinal tumor suppression by nonsteroidal antiinflammatory drugs

Colorectal tumorigenesis is driven by genetic alterations in the adenomatous polyposis coli (APC) tumor suppressor pathway and effectively inhibited by nonsteroidal antiinflammatory drugs (NSAIDs). However, how NSAIDs prevent colorectal tumorigenesis has remained obscure. We found that the extrinsic apoptotic pathway and the BH3 interacting-domain death agonist (BID) are activated in adenomas from NSAID-treated patients. Loss of BID abolishes NSAID-mediated tumor suppression, survival benefit, and apoptosis in tumor-initiating stem cells in APC(Min/+) mice. BID-mediated cross-talk between the extrinsic and intrinsic apoptotic pathways is responsible for selective killing of neoplastic cells by NSAIDs. We further demonstrate that NSAIDs induce death receptor signaling in both cancer and normal cells, but only activate BID in cells with APC deficiency and ensuing c-Myc activation. Our results suggest that NSAIDs suppress intestinal tumorigenesis through BID-mediated synthetic lethality triggered by death receptor signaling and gatekeeper mutations, and provide a rationale for developing more effective cancer prevention strategies and agents

Evaluation of a 2-1-1 Telephone Navigation Program to increase Cancer Control Behaviors: Results From a Randomized Controlled Trial

PURPOSE: to evaluate the effectiveness of a telephone navigation intervention for increasing use of cancer control services among underserved 2-1-1 callers. DESIGN: Randomized controlled trial. SETTING: 2-1-1 call centers in Houston and Weslaco, Texas (located in the Rio Grande Valley near the Mexican border). PARTICIPANTS: 2-1-1 callers in need of Pap test, mammography, colorectal cancer screening, smoking cessation counseling, and/or HPV vaccination for a daughter (n = 1,554). A majority were low-income and described themselves as Black or Hispanic. INTERVENTION: Participants were randomly assigned to receive either a cancer control referral for the needed service(s) with telephone navigation from a trained cancer control navigator (n = 995) or a referral only (n = 559). MEASURES: Uptake of each individual service and any needed service. ANALYSIS: Assessed uptake in both groups using bivariate chi-square analyses and multivariable logistic regression analyses, adjusted for sociodemographic covariates. Both per-protocol and intent-to-treat approaches were used. RESULTS: Both interventions increased cancer control behaviors. Referral with navigation intervention resulted in significantly greater completion of any needed service (OR = 1.38; p = .042), Pap test (OR = 1.56; p = .023), and smoking cessation counseling (OR = 2.66; p = .044), than referral-only condition. Other outcomes showed the same trend although the difference was not statistically significant: mammography (OR = 1.53; p = .106); colorectal cancer screening (OR = 1.80; p = .095); and HPV vaccination of a daughter (OR = 1.61; p = .331). CONCLUSION: Adding cancer control referrals and navigation to an informational service like the 2-1-1 program can increase overall participation in cancer control services

Prolonged and tunable residence time using reversible covalent kinase inhibitors.

Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an inverted orientation of the cysteine-reactive cyanoacrylamide electrophile, we identified potent and selective BTK inhibitors that demonstrated biochemical residence times spanning from minutes to 7 d. An inverted cyanoacrylamide with prolonged residence time in vivo remained bound to BTK for more than 18 h after clearance from the circulation. The inverted cyanoacrylamide strategy was further used to discover fibroblast growth factor receptor (FGFR) kinase inhibitors with residence times of several days, demonstrating the generalizability of the approach. Targeting of noncatalytic cysteines with inverted cyanoacrylamides may serve as a broadly applicable platform that facilitates 'residence time by design', the ability to modulate and improve the duration of target engagement in vivo

Ocean Futures for the World’s Largest Yellowfin Tuna Population Under the Combined Effects of Ocean Warming and Acidification

The impacts of climate change are expected to have profound effects on the fisheries of the Pacific Ocean, including its tuna fisheries, the largest globally. This study examined the combined effects of climate change on the yellowfin tuna population using the ecosystem model SEAPODYM. Yellowfin tuna fisheries in the Pacific contribute significantly to the economies and food security of Pacific Island Countries and Territories and Oceania. We use an ensemble of earth climate models to project yellowfin populations under a high greenhouse gas emissions (IPCC RCP8.5) scenario, which includes, the combined effects of a warming ocean, increasing acidification and changing ocean chemistry. Our results suggest that the acidification impact will be smaller in comparison to the ocean warming impact, even in the most extreme ensemble member scenario explored, but will have additional influences on yellowfin tuna population dynamics. An eastward shift in the distribution of yellowfin tuna was observed in the projections in the model ensemble in the absence of explicitly accounting for changes in acidification. The extent of this shift did not substantially differ when the three-acidification induced larval mortality scenarios were included in the ensemble; however, acidification was projected to weaken the magnitude of the increase in abundance in the eastern Pacific. Together with intensive fishing, these potential changes are likely to challenge the global fishing industry as well as the economies and food systems of many small Pacific Island Countries and Territories. The modelling framework applied in this study provides a tool for evaluating such effects and informing policy development

The Promise of Prediction Markets

Prediction markets are markets for contracts that yield payments based on the outcome of an uncertain future event, such as a presidential election. Using these markets as forecasting tools could substantially improve decision making in the private and public sectors. We argue that U.S. regulators should lower barriers to the creation and design of prediction markets by creating a safe harbor for certain types of small stakes markets. We believe our proposed change has the potential to stimulate innovation in the design and use of prediction markets throughout the economy, and in the process to provide information that will benefit the private sector and government alike.Technology and Industry

Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth

Blood vessels form either when dispersed endothelial cells (the cells lining the inner walls of fully-formed blood vessels) organize into a vessel network (vasculogenesis), or by sprouting or splitting of existing blood vessels (angiogenesis). Although they are closely related biologically, no current model explains both phenomena with a single biophysical mechanism. Most computational models describe sprouting at the level of the blood vessel, ignoring how cell behavior drives branch splitting during sprouting. We present a cell-based, Glazier-Graner-Hogeweg-model simulation of the initial patterning before the vascular cords form lumens, based on plausible behaviors of endothelial cells. The endothelial cells secrete a chemoattractant, which attracts other endothelial cells. As in the classic Keller-Segel model, chemotaxis by itself causes cells to aggregate into isolated clusters. However, including experimentally-observed adhesion-driven contact inhibition of chemotaxis in the simulation causes randomly-distributed cells to organize into networks and cell aggregates to sprout, reproducing aspects of both de novo and sprouting blood-vessel growth. We discuss two branching instabilities responsible for our results. Cells at the surfaces of cell clusters attempting to migrate to the centers of the clusters produce a buckling instability. In a model variant that eliminates the surface-normal force, a dissipative mechanism drives sprouting, with the secreted chemical acting both as a chemoattractant and as an inhibitor of pseudopod extension. The branching instabilities responsible for our results, which result from contact inhibition of chemotaxis, are both generic developmental mechanisms and interesting examples of unusual patterning instabilities.Comment: Thoroughly revised version, now in press in PLoS Computational Biology. 53 pages, 13 figures, 2 supporting figures, 56 supporting movies, source code and parameters files for computer simulations provided. Supporting information: http://www.psb.ugent.be/~romer/ploscompbiol/ Source code: http://sourceforge.net/projects/tst

Distinct genotypic profiles of the two major clades of Mycobacterium africanum

Background: Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis (TB) and a member of the M. tuberculosis complex (MTC). Additional MTC species that cause TB in humans and other mammals include Mycobacterium africanum and Mycobacterium bovis. One result of studies interrogating recently identified MTC phylogenetic markers has been the recognition of at least two distinct lineages of M. africanum, known as West African-1 and West African-2. Methods: We screened a blinded non-random set of MTC strains isolated from TB patients in Ghana (n = 47) for known chromosomal region-of-difference (RD) loci and single nucleotide polymorphisms (SNPs). A MTC PCR-typing panel, single-target standard PCR, multi-primer PCR, PCR-restriction fragment analysis, and sequence analysis of amplified products were among the methods utilized for the comparative evaluation of targets and identification systems. The MTC distributions of novel SNPs were characterized in the both the Ghana collection and two other diverse collections of MTC strains (n = 175 in total). Results: The utility of various polymorphisms as species-, lineage-, and sublineage-defining phylogenetic markers for M. africanum was determined. Novel SNPs were also identified and found to be specific to either M. africanum West African-1 (Rv1332 523; n = 32) or M. africanum West African-2 (nat 751; n = 27). In the final analysis, a strain identification approach that combined multi-primer PCR targeting of the RD loci RD9, RD10, and RD702 was the most simple, straight-forward, and definitive means of distinguishing the two clades of M. africanum from one another and from other MTC species. Conclusion: With this study, we have organized a series of consistent phylogenetically-relevant markers for each of the distinct MTC lineages that share the M. africanum designation. A differential distribution of each M. africanum clade in Western Africa is described