How Changes in Extracellular Matrix Mechanics and Gene Expression Variability Might Combine to Drive Cancer Progression

Changes in extracellular matrix (ECM) structure or mechanics can actively drive cancer progression; however, the underlying mechanism remains unknown. Here we explore whether this process could be mediated by changes in cell shape that lead to increases in genetic noise, given that both factors have been independently shown to alter gene expression and induce cell fate switching. We do this using a computer simulation model that explores the impact of physical changes in the tissue microenvironment under conditions in which physical deformation of cells increases gene expression variability among genetically identical cells. The model reveals that cancerous tissue growth can be driven by physical changes in the microenvironment: when increases in cell shape variability due to growth-dependent increases in cell packing density enhance gene expression variation, heterogeneous autonomous growth and further structural disorganization can result, thereby driving cancer progression via positive feedback. The model parameters that led to this prediction are consistent with experimental measurements of mammary tissues that spontaneously undergo cancer progression in transgenic C3(1)-SV40Tag female mice, which exhibit enhanced stiffness of mammary ducts, as well as progressive increases in variability of cell-cell relations and associated cell shape changes. These results demonstrate the potential for physical changes in the tissue microenvironment (e.g., altered ECM mechanics) to induce a cancerous phenotype or accelerate cancer progression in a clonal population through local changes in cell geometry and increased phenotypic variability, even in the absence of gene mutation

Making Marine Life Count: A New Baseline for Policy

The Census of Marine Life aids practical work of the Convention on Biological Diversity, discovers and tracks ocean biodiversity, and supports marine environmental planning

Uniting science and stories: Perspectives on the value of storytelling for communicating science

Science helps us identify problems, understand their extent, and begin to find solutions; it helps us understand future directions for our society. Scientists bear witness to scenes of change and discovery that most people will never experience. Yet the vividness of these experiences is often left out when scientists talk and write about their work. A growing community of practice is showing that scientists can share their message in an engaging way using a strategy that most are already familiar with: storytelling. Here we draw on our experiences leading scientist communication training and hosting science storytelling events at the International Marine Conservation Congress to share basic techniques, tips, and resources for incorporating storytelling into any scientist’s communication toolbox

Toward understanding youth athletes’ fun priorities: An investigation of sex, age, and levels of play

Colloquial conjecture asserts perceptions of difference in what is more or less important to youth athletes based on binary categorization, such as sex (girls vs. boys), age (younger vs. older), and level of competitive play (recreational vs. travel). The fun integration theory’s FUN MAPS, which identify 11 fun-factors comprised of 81 fun-determinants, offers a robust framework from which to test these conceptions related to fun. Therefore, the purposes of this study were to scientifically explore: (a) the extent to which soccer players’ prioritization of the 11 fun-factors and 81 fun-determinants were consistent with the gender differences hypothesis or the gender similarities hypothesis, and (b) how their fun priorities evolved as a function of their age and level of play. Players’ (n = 141) data were selected from the larger database that originally informed the conceptualization of the fun integration theory’s FUN MAPS. Following selection, innovative pattern match displays and go-zone displays were produced to identify discrete points of consensus and discordance between groups. Regardless of sex, age, or level of play, results indicated extraordinarily high consensus among the players’ reported importance of the fun-factors (r = .90–.97) and fun-determinants (r = .92–.93), which were consistently grouped within strata of primary, secondary, and tertiary importance. Overall, results were consistent with the gender similarities hypothesis, thereby providing the first data to dispel common conceptions about what is most fun with respect to sex, in addition to age and level of play, in a sample of youth soccer players

Relative Importance of the Fun Factors: Pattern Matched Perceptions among Players, Parents, and Coaches

Background. The FUN MAPS are evidence-based blueprints for the fun integration theory, youth sport’s first-ever stakeholder-derived, theoretical framework for promoting fun through structured skill development and competitive play (Visek et al., 2015). Developed from the direct input of players, parents, and coaches, the FUN MAPS identify and quantify the importance of 81 fun-determinants within 11 factors (i.e., Positive team dynamics, Trying hard, Positive coaching, Learning and improving, Game time support, Games, Practices, Team friendships, Mental bonuses, Team rituals, and Swag). However, the FUN MAPS are based on the combined input from players, parents, and coaches. Efforts to promote the most fun for children requires their priorities to be considered independent of adults and comparatively to one another within and across sex, age, and competition level. Additionally, to elucidate exact points of consensus/discordance between children and adults, players’ priorities should be considered alongside parents and coaches’ perceptions. Therefore, the purposes of this study were to use pattern matching displays, useful for determining within and between group differences, to identify the extent to which children’s (n = 142) reported importance of the 11 factors evolves throughout their development and how their perceptions compares to adults (parents, n = 57; coaches, n = 35). Methods. The Concept Systems® Global MAX license was used to produce pattern match displays for consensus analysis (r). Mann-Whitney U tests were used to identify the fun-factors on which groups significantly differed; and, the Fisher r-to-z transformation was used to determine whether consensus between pattern matches were significantly different from one another. Results. Results indicate remarkably high degrees of consensus among children, regardless of sex, age, and competition level comparison (r’s = .90-.97). Consensus was also high among children and parents (r = .93); however, it was significantly lower among children and coaches (r’s = .68-.93). Pattern matches are displayed using sophisticated, illustrative ladder graphs. Discussion. Novel findings from this study provide a more complete context for understanding children’s fun priorities across all 11 fun-factors. Overall, with respect to players, results support the gender similarities hypothesis, rather than the gender differences hypothesis and the other age and competition level assumptions that have long guided organized youth sport. The discordance observed between older players and coaches is of great concern to children’s continued participation into adolescence and may account for the dramatic dropout that occurs around the age of 13. Best practices for optimizing children’s fun sport experiences are forwarded

Using bisphosphonates to control the pain of bone metastases: evidence-based guidelines for palliative care.

This work was undertaken by the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland (APM) as a demonstration project in developing clinical guidelines relevant to palliative care from a pragmatic approach to literature review and grading of clinical evidence. CANCERLIT and Embase were searched for relevant papers written in English, published since 1980. Each study identified was rated against agreed criteria for levels of evidence. Most studies were not specifically designed to define speed of response, and were not undertaken in palliative care patients. Thus, careful reading and grading of each study was necessary. Sufficient evidence was identified to make recommendations for clinical practice in a palliative care population of patients, and areas for future research have been identified. Bisphosphonates appear to have a role in managing pain from metastases which has been refractory to conventional analgesic management and where oncological or orthopaedic intervention is delayed or inappropriate

Heterogeneous tumor formation in 16-week-old mammary glands of FVB C3(1)-SV40Tag transgenic mice that contained ducts displaying the morphology of normal epithelium, hyperplastic epithelium, and DCIS lesions.

<p>(<b>A</b>) Tumor cell proliferation (PCNA) and differentiation (ERα and PR) were altered in hyperplastic and DCIS ducts compared to normal ducts whereas the transgene expression remained similar (SV40). Scale bar: 20 µm. (<b>B–D</b>) Morphometric analysis of ductal heterogeneity (N, normal; H, hyperplastic; D, DCIS). (<b>B</b>) Epithelial cell growth (% PCNA-positive cells) increased slightly, but significantly in DCIS ducts compared to normal ducts whereas the percentage of cells expressing (<b>C</b>) ERα and (<b>D</b>) PR decreased significantly in DCIS ducts compared to normal (*, <i>p</i><0.05).</p

Cell shape and mechanical changes accompany cancer progression in FVB C3(1)-SV40Tag transgenic mice.

<p>(<b>A</b>) Regional variations in mammary cancer progression observed in the same mammary gland isolated from a 16-week-old transgenic mouse. Note that normal ducts (<b>N</b>), hyperplastic ducts (<b>H</b>) and DCIS-resembling ducts (<b>D</b>) can be found in close proximity in the same gland (scale bar: 100 µm). (<b>B</b>) High magnification H&E stainings of normal, hyperplastic and DCIS ducts in 16-week-old transgenic females highlighting epithelial cell shape changes that accompany cancer progression when cells become increasingly pleiomorphic. (<b>C</b>) Histograms showing the Young’s moduli of epithelium and periductal stroma of different normal and DCIS ducts measured within the same 16-week-old transgenic mammary glands using AFM. (<b>D</b>) Average stiffnesses measured in the epithelial and stromal compartments of normal versus DCIS ducts within the same 16-week-old glands (*, <i>p</i><0.05).</p