Islands of conformational stability for Filopodia

Filopodia are long, thin protrusions formed when bundles of fibers grow outwardly from a cell surface while remaining closed in a membrane tube. We study the subtle issue of the mechanical stability of such filopodia and how this depends on the deformation of the membrane that arises when the fiber bundle adopts a helical configuration. We calculate the ground state conformation of such filopodia, taking into account the steric interaction between the membrane and the enclosed semiflexible fiber bundle. For typical filopodia we find that a minimum number of fibers is required for filopodium stability. Our calculation elucidates how experimentally observed filopodia can obviate the classical Euler buckling condition and remain stable up to several tens of . We briefly discuss how experimental observation of the results obtained in this work for the helical-like deformations of enclosing membrane tubes in filopodia could possibly be observed in the acrosomal reactions of the sea cucumber Thyone, and the horseshoe crab Limulus. Any realistic future theories for filopodium stability are likely to rely on an accurate treatment of such steric effects, as analysed in this work

Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring

Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase (ALDH) family 1 is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease, used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential, and readily translatable, antifibrotic therapy

Fixation Prediction and Visual Priority Maps for Biped Locomotion

© 2017 IEEE. This paper presents an analysis of the low-level features and key spatial points used by humans during locomotion over diverse types of terrain. Although, a number of methods for creating saliency maps and task-dependent approaches have been proposed to estimate the areas of an image that attract human attention, none of these can straightforwardly be applied to sequences captured during locomotion, which contain dynamic content derived from a moving viewpoint. We used a novel learning-based method for creating a visual priority map informed by human eye tracking data. Our proposed priority map is created based on two fixation types: first exploiting the observation that humans search for safe foot placement and second that they observe the edges of a path as a guide to safe traversal of the terrain. Texture features and the difference between them, observed at the region around an eye position, are employed within a support vector machine to create a visual priority map for biped locomotion. The results show that our proposed method outperforms the state-of-the-art, particularly for more complex terrains, where achieving smooth locomotion needs more attention on the traversing path

“What’s on the Test?”: The Impact of Giving Students a Concept-List Study Guide

Students frequently request concept-list study guides prior to exams, but the benefits of instructors providing such resources are unclear. Research on memory and comprehension has suggested that some challenges in learning are associated with benefits to performance. In the context of an introductory psychology course, a study was conducted to investigate the impact of providing a concept-list study guide on exam performance, as opposed to having students create a study guide. Additionally, student preferences for various types of study guides were examined. Results indicated that although students greatly prefer that the instructors provide a study guide (as opposed to making their own), providing a concept-list study guide resulted in poorer exam performance. These results call for future research on the influence of study guides on student performance

Addressing Inequity to Achieve the Maternal and Child Health Millennium Development Goals: Looking Beyond Averages.

Inequity in access to and use of child and maternal health interventions is impeding progress towards the maternal and child health Millennium Development Goals. This study explores the potential health gains and equity impact if a set of priority interventions for mothers and under fives were scaled up to reach national universal coverage targets for MDGs in Tanzania. We used the Lives Saved Tool (LiST) to estimate potential reductions in maternal and child mortality and the number of lives saved across wealth quintiles and between rural and urban settings. High impact maternal and child health interventions were modelled for a five-year scale up, by linking intervention coverage, effectiveness and cause of mortality using data from Tanzania. Concentration curves were drawn and the concentration index estimated to measure the equity impact of the scale up. In the poorest population quintiles in Tanzania, the lives of more than twice as many mothers and under-fives were likely to be saved, compared to the richest quintile. Scaling up coverage to equal levels across quintiles would reduce inequality in maternal and child mortality from a pro rich concentration index of -0.11 (maternal) and -0.12 (children) to a more equitable concentration index of -0,03 and -0.03 respectively. In rural areas, there would likely be an eight times greater reduction in maternal deaths than in urban areas and a five times greater reduction in child deaths than in urban areas. Scaling up priority maternal and child health interventions to equal levels would potentially save far more lives in the poorest populations, and would accelerate equitable progress towards maternal and child health MDGs

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Long-term burden of increased body mass index from childhood on adult dyslipidemia: the i3C Consortium study

Background: Data are limited regarding the association of cumulative burden and trajectory of body mass index (BMI) from early life with adult lipid disorders. Methods: The study cohort consisted of 5195 adults who had BMI repeatedly measured 4 to 21 times from childhood and had blood lipid measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and information on lipid-lowering medications in the last adult survey. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI. Results: Participants with dyslipidemia, high LDL-C, low HDL-C and high TG had consistently and significantly higher BMI levels from childhood to adulthood compared to those with normal lipid levels. After adjusting for age, race, sex, and cohort, increased risk of adult dyslipidemia was significantly associated with higher values of childhood BMI, adulthood BMI, total AUC and incremental AUC, with odds ratio (95% confidence interval) = 1.22 (1.15-1.29), 1.85 (1.74-1.97), 1.61 (1.52-1.71), and 1.59 (1.50-1.69), respectively, and p Conclusions: Adults with dyslipidemia versus normal lipid levels have consistently higher levels and distinct life-course trajectories of BMI, suggesting that the impact of excessive body weight on dyslipidemia originates in early life

Childhood/adolescent smoking and adult smoking and cessation: The International Childhood Cardiovascular Cohort (i3C) Consortium

Background: Despite declining US adolescent smoking prevalence from 40% among 12th graders in 1995 to around 10% in 2018, adolescent smoking is still a significant problem. Using the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes 7 international cohorts recruited in childhood and followed into adulthood, the present study was designed to confirm the important relation between adolescent smoking and daily adult smoking and present new data on adult smoking into the forties and comparison of smoking in the United States, Finland, and Australia. Methods and Results: Childhood smoking experience during ages 6 to 19 in the 1970s and 1980s was classifiable in 6687 i3C participants who also provided smoking status in their twenties and forties through 2011-2018. Prevalence of daily smoking in their twenties was directly related to degree of smoking during adolescence and inversely related to the age at which that smoking experience occurred (P trend, P trend, Conclusions: These long-term follow-up data show that smoking intensity increased throughout adolescence. Prevalence of adult smoking and cessation by the forties were both correlated with levels of childhood smoking intensity. These data lend support to preventive strategies designed to reduce, delay, or eliminate any youth access to cigarettes

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs