A microRNA Imparts Robustness against Environmental Fluctuation during Development

The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some of the genes that it regulates in Drosophila are not regulated in mammals. We have explored the role of lineage restricted targets, using Drosophila , in order to better understand the evolutionary significance of microRNA-target relationships. From studies of two well characterized developmental regulatory networks, we find that miR-7 functions in several interlocking feedback and feedforward loops, and propose that its role in these networks is to buffer them against perturbation. To directly demonstrate this function for miR-7, we subjected the networks to temperature fluctuation and found that miR-7 is essential for the maintenance of regulatory stability under conditions of environmental flux. We suggest that some conserved microRNAs like miR-7 may enter into novel genetic relationships to buffer developmental programs against variation and impart robustness to diverse regulatory networks

Violence, alcohol and symptoms of depression and in Cape Town's poorest communities: results of a community survey

Introduction This paper summarises key findings from the first of three household surveys conducted in three high-violence areas in the Cape Town, investigating community members’ experiences of alcohol use, their built environment, violence and symptoms of depression, together with their views on alcohol and other interventions. Methods A stratified random sample of 1500 dwellings, 1200 in Khayelitsha and 300 in Gugulethu and Nyanga (“Gunya”) was selected using GIS address data for formal areas and aerial photography for informal areas. Fieldwork took place from July to November 2013. Responses to questions were summarized by area, gender, age and formal vs. informal settlement type. Results After substitution and data cleaning, 1213 Khayelitsha households and 286 Gunya households were included. In Gunya, 29% of respondents reported that they or their family members had been affected by at least one violent crime (murder, assault, domestic violence, rape) in the past year, compared with 12% in Khayelitsha. Using a CES-D-10 cut-off of 10, 44% of respondents were classified as depressed. More than half the respondents reported having experienced some form of alcohol nuisance. Respondents were supportive of alcohol interventions such as increased taxes and police regulation of outlets, particularly in Gunya (87%) and amongst female respondents (76%). Satisfaction with infrastructure such as street lighting and drainage was generally low. Conclusions The results describe the co-occurring burdens of alcohol and drug use, violence, depression and deprivation in our study populations

Repressive gene regulation synchronizes development with cellular metabolism

Metabolic conditions affect the developmental tempo of animals. Developmental gene regulatory networks (GRNs) must therefore synchronize their dynamics with a variable timescale. We find that layered repression of genes couples GRN output with variable metabolism. When repressors of transcription or mRNA and protein stability are lost, fewer errors in Drosophila development occur when metabolism is lowered. We demonstrate the universality of this phenomenon by eliminating the entire microRNA family of repressors and find that development to maturity can be largely rescued when metabolism is reduced. Using a mathematical model that replicates GRN dynamics, we find that lowering metabolism suppresses the emergence of developmental errors by curtailing the influence of auxiliary repressors on GRN output. We experimentally show that gene expression dynamics are less affected by loss of repressors when metabolism is reduced. Thus, layered repression provides robustness through error suppression and may provide an evolutionary route to a shorter reproductive cycle

Inequities in Access to Quality Early Care and Education: Associations with Funding and Community Context

The purpose of the current study was to examine program- and community-level characteristics related to total points earned by early care and education programs in North Carolina’s Tiered Quality Rating and Improvement System (TQRIS). Multiple statewide data sources, program- and community-level characteristics were combined to better understand associations with total points awarded in the TQRIS. The concentration of state and federal funding at the program level, and the socioeconomics of the communities that programs resided were related to program quality. The current study demonstrated that there are inequities within the system where the highest quality early care and education programs are differentially available based on program funding characteristics, community socioeconomics, and interactions among the program and community variables. Future research and policy implications are discussed.Keywords: Community context, Child care quality, Quality Rating and Improvement System, Socioeconomics, State and federal fundingKeywords: Community context, Child care quality, Quality Rating and Improvement System, Socioeconomics, State and federal fundin

Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces – the role of focal adhesion maturation

The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society. Hence, there is a need for next generation implantable devices to substitute for, or guide, bone repair in vivo. Cellular responses to nanometric topographical cues need to be better understood in vitro in order to ensure the effective and efficient integration and performance of these orthopaedic devices. In this study, the FDA approved plastic polycaprolactone, was embossed with nanometric grooves and the response of primary and immortalised osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 μm wide. Cells cultured on test surfaces followed contact guidance along the length of groove edges, elongated along their major axis and showed nuclear distortion, they formed more focal complexes and a lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalised cells was observed on grooved substrates. Down-regulation appeared to directly correlate with focal adhesion maturation, indicating the involvement of ERK 1/2 negative feedback pathways following integrin mediated FAK activation

Primary physical education, coaches and continuing professional development

This is an Author's Accepted Manuscript of an article published in Sport, Education and Society, 16(4), 485 - 505, 2011, copyright @ Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/13573322.2011.589645.Physical education (PE) in primary schools has traditionally been taught by qualified primary teachers. More recently, some teaching of PE in primary schools has been undertaken by coaches (mostly football coaches). These coaches hold national governing body awards but do not hold teaching qualifications. Thus, coaches may not be adequately prepared to teach PE in curriculum time. The purpose of this study was to evaluate the perceptions of a group of community-based football coaches working in primary schools for the impact of a Continuing Professional Development (CPD) programme on their ability to undertake ‘specified work’ to cover PE in primary schools. The programme focused on four areas identified as important to enable coaches to cover specified work: short- and medium-term planning, pedagogy, knowledge of the curriculum and reflection. Results showed that for the majority of coaches the CPD programme had made them more aware of the importance of these four areas and had helped to develop their knowledge and ability to put this into practice in covering planning, preparation and assessment time. However, further input is still required to develop coaches’ knowledge and understanding in all four areas, but especially their curriculum knowledge, as well as their ability to put these into practice consistently. These findings are discussed in relation to the implications of employing coaches to cover the teaching of PE in primary schools and, if employed, what CPD coaches need to develop the necessary knowledge, skill and understanding for covering specified work in schools

Radiatively driven hypersonic wind tunnel

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76604/1/AIAA-12568-479.pd

A Self-Consistent Vacuum for Misner Space and the Chronology Protection Conjecture

In this paper we find a self-consistent vacuum for Misner space. For this "adapted" Rindler vacuum the renormalized stress-energy tensor is zero throughout the Misner space. A point-like particle detector traveling on a timelike geodesic in a Misner space with this vacuum detects nothing. Misner space with this vacuum thus creates no problems for time travel in and of itself but a time traveler may pose a danger to himself and to the spacetime.Comment: 5 pages, received September 5, 1997, with a note added November 24, 199

Stability of asymmetric tetraquarks in the minimal-path linear potential

The linear potential binding a quark and an antiquark in mesons is generalized to baryons and multiquark configurations as the minimal length of flux tubes neutralizing the color, in units of the string tension. For tetraquark systems, i.e., two quarks and two antiquarks, this involves the two possible quark--antiquark pairings, and the Steiner tree linking the quarks to the antiquarks. A novel inequality for this potential demonstrates rigorously that within this model the tetraquark is stable in the limit of large quark-to-antiquark mass ratio.Comment: 8 pages, 6 figures, pdflate

Can the Universe Create Itself?

The question of first-cause has troubled philosophers and cosmologists alike. Now that it is apparent that our universe began in a Big Bang explosion, the question of what happened before the Big Bang arises. Inflation seems like a very promising answer, but as Borde and Vilenkin have shown, the inflationary state preceding the Big Bang must have had a beginning also. Ultimately, the difficult question seems to be how to make something out of nothing. This paper explores the idea that this is the wrong question --- that that is not how the Universe got here. Instead, we explore the idea of whether there is anything in the laws of physics that would prevent the Universe from creating itself. Because spacetimes can be curved and multiply connected, general relativity allows for the possibility of closed timelike curves (CTCs). Thus, tracing backwards in time through the original inflationary state we may eventually encounter a region of CTCs giving no first-cause. This region of CTCs, may well be over by now (being bounded toward the future by a Cauchy horizon). We illustrate that such models --- with CTCs --- are not necessarily inconsistent by demonstrating self-consistent vacuums for Misner space and a multiply connected de Sitter space in which the renormalized energy-momentum tensor does not diverge as one approaches the Cauchy horizon and solves Einstein's equations. We show such a Universe can be classically stable and self-consistent if and only if the potentials are retarded, giving a natural explanation of the arrow of time. Some specific scenarios (out of many possible ones) for this type of model are described. For example: an inflationary universe gives rise to baby universes, one of which turns out to be itself. Interestingly, the laws of physics may allow the Universe to be its own mother.Comment: 48 pages, 8 figure