Plasticity of differentiated cells in wound repair and tumorigenesis, Part II: Skin and intestine

Recent studies have identified and begun to characterize the roles of regenerative cellular plasticity in many organs. In Part I of our two-part Review, we discussed how cells reprogram following injury to the stomach and pancreas. We introduced the concept of a conserved cellular program, much like those governing division and death, which may allow mature cells to become regenerative. This program, paligenosis, is likely necessary to help organs repair the numerous injuries they face over the lifetime of an organism; however, we also postulated that rounds of paligenosis and redifferentiation may allow long-lived cells to accumulate and store oncogenic mutations, and could thereby contribute to tumorigenesis. We have termed the model wherein differentiated cells can store mutations and then unmask them upon cell cycle re-entry the ‘cyclical hit’ model of tumorigenesis. In the present Review (Part II), we discuss these concepts, and cell plasticity as a whole, in the skin and intestine. Although differentiation and repair are arguably more thoroughly studied in skin and intestine than in stomach and pancreas, it is less clear how mature skin and intestinal cells contribute to tumorigenesis. Moreover, we conclude our Review by discussing plasticity in all four organs, and look for conserved mechanisms and concepts that might help advance our knowledge of tumor formation and advance the development of therapies for treating or preventing cancers that might be shared across multiple organs

Design and construction of a Modular NaI(Tl) Detector Array for use in the Parity- and Time Reversal Violation Measurements for NOPTREX

The goal of the NOPTREX collaboration is to probe the Standard Model by utilizing the properties of low energy neutron-nucleus resonances to find evidence of parity- and time-reversal-odd violations. In order to conduct these sensitive experiments, it is needed to design and simulate an array of modular, high precision NaI(Tl) detectors. These detectors will be designed to operate in both pulse and current modes. We have tentative beam time at LANSCE to perform a search for new parity violation in heavy nuclei as candidates for time reversal and to perform a research and development effort on the n+d=t+gamma experiment. We will discuss the results of our experiments to determine the most efficient design of the detectors, electronics, and magnetic shielding, as well as our progress on the construction and characterization of the array

Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice

Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmp1-Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmp1 gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, Dmp1-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, Cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, Dmp1-Cre marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express Pdgfra. Confirming the utility of Dmp1-Cre in the gastrointestinal mesenchyme, deletion of Bmpr1a with Dmp1-Cre causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when using Dmp1-Cre because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types

First aid knowledge retention in school children: A review of the literature

Introduction First aid training for lay people is recognised as an important capacity building component of pre-hospital care in communities. In countries such as Australia, this training is increasingly targeted to school children, but relatively little attention is directed to knowledge retention or optimal training methods for this population. This literature review aimed to determine whether the published literature demonstrates that first aid knowledge is retained by school children who have learnt first aid from professional first aid providers. Methods A systematic search of the peer-reviewed and grey literature was conducted for narrative review. Journal articles were retrieved from three databases (MEDLINE, CINAHL, ERIC) using the search terms ‘first aid’; ‘resuscitation’; ‘training’; ‘child*’; and ‘school’. Inclusion and exclusion criteria were applied and review findings organised thematically. Results The search yielded four primary studies of European school children aged between 4 and 12 years trained by professional first aid providers. Subsequent review identified emergent themes of Resuscitative first aid and Non-resuscitative first aid. Heterogeneity was apparent in training and evaluation methods, and study quality varied. Reported first aid knowledge retention was mixed. Conclusion There is a lack of quality evidence to guide optimal training methods and maximise first aid knowledge retention in school children. To date, research in this area has been limited to Europe. Further research is therefore recommended. Formal evaluation of professional first aid training can help guide training methods and enhance first aid knowledge retention in school children, thereby building more robust first aid capacity in the community

GOurmet: A tool for quantitative comparison and visualization of gene expression profiles based on gene ontology (GO) distributions

BACKGROUND: The ever-expanding population of gene expression profiles (EPs) from specified cells and tissues under a variety of experimental conditions is an important but difficult resource for investigators to utilize effectively. Software tools have been recently developed to use the distribution of gene ontology (GO) terms associated with the genes in an EP to identify specific biological functions or processes that are over- or under-represented in that EP relative to other EPs. Additionally, it is possible to use the distribution of GO terms inherent to each EP to relate that EP as a whole to other EPs. Because GO term annotation is organized in a tree-like cascade of variable granularity, this approach allows the user to relate (e.g., by hierarchical clustering) EPs of varying length and from different platforms (e.g., GeneChip, SAGE, EST library). RESULTS: Here we present GOurmet, a software package that calculates the distribution of GO terms represented by the genes in an individual expression profile (EP), clusters multiple EPs based on these integrated GO term distributions, and provides users several tools to visualize and compare EPs. GOurmet is particularly useful in meta-analysis to examine EPs of specified cell types (e.g., tissue-specific stem cells) that are obtained through different experimental procedures. GOurmet also introduces a new tool, the Targetoid plot, which allows users to dynamically render the multi-dimensional relationships among individual elements in any clustering analysis. The Targetoid plotting tool allows users to select any element as the center of the plot, and the program will then represent all other elements in the cluster as a function of similarity to the selected central element. CONCLUSION: GOurmet is a user-friendly, GUI-based software package that greatly facilitates analysis of results generated by multiple EPs. The clustering analysis features a dynamic targetoid plot that is generalizable for use with any clustering application

Tumor organoids to study gastroesophageal cancer: A primer

Gastroesophageal cancers are leading causes of cancer death. Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and pathways. It is clear that we should no longer treat all gastroesophageal cancers as a homogeneous disease, which is what we do when we use non-specific chemotherapy. However, we currently cannot monitor successful gene/pathway targeting, nor understand how/when tumors develop resistance, nor predict which patients will derive maximal benefit. To improve outcomes, we must precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well as develop novel avenues to study and predict treatment effects in individual patients. To this end, patient-derived organoids, in which tumor cells from individual patients are grown in a Petri dish, are a new versatile system that allows for timely expandability, detailed molecular characterization, and genetic manipulation with the promise of enabling predictive assessment of treatment response. In this review, we will explore the development and basic techniques for organoid generation, and discuss the current and potential future applications of this exciting technology to study the basic science of carcinogenesis and to predict/guide cancer patient care in the clinics

Adaptation without natural selection

Document is itself an extended abstract

St. Norbert College as Arboretum: Mapping the Trees on Campus

St. Norbert College as Arboretum: Mapping the Trees on Campus - Take a virtual tour of the trees on campus. The tour is a multimedia ArcGIS Online story map and is available here. Many of the trees on the St. Norbert Campus were planted by Fr. Anselm Keefe (1895- 1974) in the mid 20th century. It was Fr. Keefe’s vision to beautify the campus by creating gardens that were accessible to the public. This included planting a diverse variety of trees, including one of every tree species native to Wisconsin. It was Keefe’s mission to make St. Norbert College an arboretum; a public garden where people could come and enjoy a diverse range of trees and other plants.https://digitalcommons.snc.edu/gis_library/1001/thumbnail.jp

If you can't be with the one you love, love the one you're with: How individual habituation of agent interactions improves global utility

Simple distributed strategies that modify the behaviour of selfish individuals in a manner that enhances cooperation or global efficiency have proved difficult to identify. We consider a network of selfish agents who each optimise their individual utilities by coordinating (or anti-coordinating) with their neighbours, to maximise the pay-offs from randomly weighted pair-wise games. In general, agents will opt for the behaviour that is the best compromise (for them) of the many conflicting constraints created by their neighbours, but the attractors of the system as a whole will not maximise total utility. We then consider agents that act as 'creatures of habit' by increasing their preference to coordinate (anti-coordinate) with whichever neighbours they are coordinated (anti-coordinated) with at the present moment. These preferences change slowly while the system is repeatedly perturbed such that it settles to many different local attractors. We find that under these conditions, with each perturbation there is a progressively higher chance of the system settling to a configuration with high total utility. Eventually, only one attractor remains, and that attractor is very likely to maximise (or almost maximise) global utility. This counterintutitve result can be understood using theory from computational neuroscience; we show that this simple form of habituation is equivalent to Hebbian learning, and the improved optimisation of global utility that is observed results from wellknown generalisation capabilities of associative memory acting at the network scale. This causes the system of selfish agents, each acting individually but habitually, to collectively identify configurations that maximise total utility