Defining key concepts of intestinal and epithelial cancer biology through the use of mouse models

Over the past 20 years, huge advances have been made in modelling human diseases such as cancer using genetically modified mice. Accurate in vivo models are essential to examine the complex interaction between cancer cells, surrounding stromal cells, tumour-associated inflammatory cells, fibroblast and blood vessels, and to recapitulate all the steps involved in metastasis. Elucidating these interactions in vitro has inherent limitations, and thus animal models are a powerful tool to enable researchers to gain insight into the complex interactions between signalling pathways and different cells types. This review will focus on how advances in in vivo models have shed light on many aspects of cancer biology including the identification of oncogenes, tumour suppressors and stem cells, epigenetics, cell death and context dependent cell signalling

The intersection of gender, social class, and cultural context: a meta-analysis

Expectancy value theory is often evoked by educational psychologists to explain gender differences in Science, Technology, Engineering, and Mathematics (STEM) variables. Yet gender does not operate in isolation. Nor are gender effects likely to be context free. In the current meta-analysis, we explore gender differences in STEM-related expectancy for success, and the task values of intrinsic, utility, attainment, and cost. We find that gender differences were generally small in size. Invoking the concept of intersectionality, we find that heterogeneity in gender effect sizes are large and gender differences are moderated, primarily, by socioeconomic status, ethnic diversity, and somewhat by national gender equalit

Osteosclerosis in the extinct Cayaoa Bruneti (Aves, anseriformes) : insights on behavior and fligftlessness

Fil: Mendoza, Ricardo de. División Paleontología Vertebrados. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La PlataFil: Tambussi, Claudia Patricia. Centro de Investigaciones en Ciencias de la Tierra (CICTERRA). Universidad Nacional de Córdoba; Argentin

The role of religion in the longer-range future, April 6, 7, and 8, 2006

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This conference that took place during April 6, 7, and 8, 2006. Co-organized by David Fromkin, Director, Frederick S. Pardee Center for the Study of the Longer-Range Future, and Ray L. Hart, Dean ad interim Boston University School of TheologyThe conference brought together some 40 experts from various disciplines to ponder upon the “great dilemma” of how science, religion, and the human future interact. In particular, different panels looked at trends in what is happening to religion around the world, questions about how religion is impacting the current political and economic order, and how the social dynamics unleashed by science and by religion can be reconciled.Carnegie Council on Ethics and International Affair

Exploring the context of sedentary behaviour in older adults (what, where, why, when and with whom)

BACKGROUND: Older adults are the most sedentary segment of the population. Little information is available about the context of sedentary behaviour to inform guidelines and intervention. There is a dearth of information about when, where to intervene and which specific behaviours intervention should target. The aim of this exploratory study was to obtain objective information about what older adults do when sedentary, where and when they are sedentary and in what social context. METHODS: The study was a cross-sectional data collection. Older adults (Mean age = 73.25, SD ± 5.48, median = 72, IQR = 11) volunteers wore activPAL monitors and a Vicon Revue timelapse camera between 1 and 7 days. Periods of sedentary behaviour were identified using the activPAL and the context extracted from the pictures taken during these periods. Analysis of context was conducted using the Sedentary Behaviour International Taxonomy classification system. RESULTS: In total, 52 days from 36 participants were available for analysis. Participants spent 70.1 % of sedentary time at home, 56.9 % of sedentary time on their own and 46.8 % occurred in the afternoon. Seated social activities were infrequent (6.9 % of sedentary bouts) but prolonged (18 % of sedentary time). Participants appeared to frequently have vacant sitting time (41 % of non-screen sedentary time) and screen sitting was prevalent (36 % of total sedentary time). CONCLUSIONS: This study provides valuable information to inform future interventions to reduce sedentary behaviour. Interventions should consider targeting the home environment and focus on the afternoon sitting time, though this needs confirmation in a larger study. Tackling social isolation may also be a target to reduce sedentary time

Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation

Objective: Colorectal cancer (CRC) is a major contributor to cancer mortality and morbidity. LIM kinase 2 (LIMK2) promotes tumour cell invasion and metastasis. The objectives of this study were to determine how LIMK2 expression is associated with CRC progression and patient outcome, and to use genetically modified Drosophila and mice to determine how LIMK2 deletion affects gastrointestinal stem cell regulation and tumour development.<p></p> Design: LIMK2 expression and activity were measured by immunostaining tumours from CRC-prone mice, human CRC cell lines and 650 human tumours. LIMK knockdown in Drosophila or Limk2 deletion in mice allowed for assessment of their contributions to gastrointestinal stem cell homeostasis and tumour development.<p></p> Results: LIMK2 expression was reduced in intestinal tumours of cancer-prone mice, as well as in human CRC cell lines and tumours. Reduced LIMK2 expression and substrate phosphorylation were associated with shorter patient survival. Genetic analysis in Drosophila midgut and intestinal epithelial cells isolated from genetically modified mice revealed a conserved role for LIMK2 in constraining gastrointestinal stem cell proliferation. Limk2 deletion increased colon tumour size in a colitis-associated colorectal mouse cancer model.<p></p> Conclusions: This study revealed that LIMK2 expression and activity progressively decrease with advancing stage, and supports the hypothesis that there is selective pressure for reduced LIMK2 expression in CRC to relieve negative constraints imposed upon gastrointestinal stem cells.<p></p&gt

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

Modelling the spatiotemporal change of canopy urban heat islands

This study models the spatiotemporal change of Birmingham’s urban heat island (UHI) using air temperature measurements made during the HiTemp project to study the atmospheric conditions over the city [1]. The study identifies the causative factors and their contributions to the formation of UHI, based on a number of data used to build 2.5 D model; land cover, land use, geometrical factors and shadow layers. The raw air temperature measurements were filtered, georeferenced and interpolated to create maps of temperature variations. The expected influencing parameters on the development of the UHI were derived and prepared for regression modelling. The results showed that the difference in temperature across Birmingham city through two years of ground measurements (June 2012 – June 2014) reached up to 13.53 °C. The UHI’s appeared daytime and night-time throughout the different seasons for approximately 56% of the total hours during the study period. However, the high intensity events happened during the calm and clear nights. Moreover, buildings’ shadow provided up to 2 °C reduction to the air temperature, while the wind speed and direction are responsible for the size and distribution of hot spots. The built up area contributed to increase the UHI, whereas, the other types of land cover and the geometrical parameters, contributed less

The Postcranial Skeleton of an Exceptionally Complete Individual of the Plated Dinosaur Stegosaurus stenops (Dinosauria: Thyreophora) from the Upper Jurassic Morrison Formation of Wyoming, U.S.A.

Copyright: © 2015 Maidment et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article