Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks

Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (approximate to 20% for one crosstalk interaction) and remain dynamically modular. The likelihood that cross-linked FFLs are dynamically correlated increases monotonically with additional crosstalk, but is independent of the specific regulation type or connectivity of the interactions. Just one additional regulatory interaction is sufficient to drive the FFL dynamics to a statistically different state. Despite the potential for modularity between sparsely connected network motifs, Escherichia coli (E. coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs remains modular. A gene ontology analysis reveals that stress response processes are significantly overrepresented in the cross-linked motifs found within E. coli. Although the daunting complexity of biological networks affects the dynamical properties of individual network motifs, some resist and remain modular, seemingly insulated from extrinsic perturbations-an intriguing possibility for nature to consistently and reliably provide certain network functionalities wherever the need arise

Prevalence of working smoke alarms in local authority inner city housing: randomised controlled trial

Objectives To identify which type of smoke alarm is most likely to remain working in local authority inner city housing, and to identify an alarm tolerated in households with smokers. Design Randomised controlled trial. Setting Two local authority housing estates in inner London. Participants 2145 households. Intervention Installation of one of five types of smoke alarm (ionisation sensor with a zinc battery; ionisation sensor with a zinc battery and pause button; ionisation sensor with a lithium battery and pause button; optical sensor with a lithium battery; or optical sensor with a zinc battery). Main outcome measure Percentage of homes with any working alarm and percentage in which the alarm installed for this study was working after 15 months. Results 54.4% (1166/2145) of all households and 45.9% (465/1012) of households occupied by smokers had a working smoke alarm. Ionisation sensor, lithium battery, and there being a smoker in the household were independently associated with whether an alarm was working (adjusted odds ratios 2.24 (95% confidence interval 1.75 to 2.87), 2.20 (1.77 to 2.75), and 0.62 (0.52 to 0.74)). The most common reasons for non-function were missing battery (19%), missing alarm (17%), and battery disconnected (4%). Conclusions Nearly half of the alarms installed were not working when tested 15 months later. Type of alarm and power source are important determinants of whether a household had a working alarm

Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation.

Women exposed to a variety of viral and bacterial infections during pregnancy have an increased risk of giving birth to a child with autism, schizophrenia or other neurodevelopmental disorders. Preclinical maternal immune activation (MIA) models are powerful translational tools to investigate mechanisms underlying epidemiological links between infection during pregnancy and offspring neurodevelopmental disorders. Our previous studies documenting the emergence of aberrant behavior in rhesus monkey offspring born to MIA-treated dams extends the rodent MIA model into a species more closely related to humans. Here we present novel neuroimaging data from these animals to further explore the translational potential of the nonhuman primate MIA model. Nine male MIA-treated offspring and 4 controls from our original cohort underwent in vivo positron emission tomography (PET) scanning at approximately 3.5-years of age using [18F] fluoro-l-m-tyrosine (FMT) to measure presynaptic dopamine levels in the striatum, which are consistently elevated in individuals with schizophrenia. Analysis of [18F]FMT signal in the striatum of these nonhuman primates showed that MIA animals had significantly higher [18F]FMT index of influx compared to control animals. In spite of the modest sample size, this group difference reflects a large effect size (Cohen's d = 0.998). Nonhuman primates born to MIA-treated dams exhibited increased striatal dopamine in late adolescence-a hallmark molecular biomarker of schizophrenia. These results validate the MIA model in a species more closely related to humans and open up new avenues for understanding the neurodevelopmental biology of schizophrenia and other neurodevelopmental disorders associated with prenatal immune challenge

Emerging Trends in Lifelong Learning: The Covenant University Perspective

In the last few decades, lifelong concept of education has resonated with other concepts such as the knowledge society, new knowledge economy, open courseware, open source, wikieconomics, and technology enabled learning. Embedded in all of these concepts and emerging from them is the notion that access to knowledge and learning is a universal right. Infact, knowledge is increasingly regarded as the solution to individual and collective, social and economic problems. In other words, lifelong learning is an essential part in the community development process, where community members acquire their life skills, soft skills and vocational skills throughout their lifespan to take part in their social, cultural, vocational and professional life. It is indeed an intervention tool for socioeconomic empowerment in a globalizing world to stay ahead in a competitive world with knowledge superiority. In this connection, the purpose of this paper is to share the lifelong learning management experience of Covenant University in terms of its programmes, processes and strategies adopted to cope with some internal and external constraints within the context of key global trends in lifelong learning. This may be of value to lifelong learning community because Covenant University is already becoming a global brand in higher education. The idea is to provide some lessons for global lifelong learning managers as well as expose them to issues and challenges confronting lifelong learning in our own part of the globe. This exposure will further show how lifelong learning has been planned, not only to bridge the knowledge gaps between university curricula corporate practices, but also between information rich and information poor citizens, particularly for the citizens who cannot afford formal education due to socio-economic backwardness

Physical Activity Minimum Threshold Predicting Improved Function in Adults With Lower‐Extremity Symptoms

Objective To identify an evidence‐based minimum physical activity threshold to predict improved or sustained high function for adults with lower‐extremity joint symptoms. Methods Prospective multisite data from 1,629 adults, age ≥49 years with symptomatic lower‐extremity joint pain/aching/stiffness, participating in the Osteoarthritis Initiative accelerometer monitoring substudy were clinically assessed 2 years apart. Improved/high function in 2‐year gait speed and patient‐reported outcomes (PROs) were based on improving or remaining in the best (i.e., maintaining high) function quintile compared to baseline status. Optimal thresholds predicting improved/high function were investigated using classification trees for the legacy federal guideline metric requiring 150 minutes/week of moderate‐vigorous (MV) activity in bouts lasting 10 minutes or more (MV‐bout) and other metrics (total MV, sedentary, light intensity activity, nonsedentary minutes/week). Results Optimal thresholds based on total MV minutes/week predicted improved/high function outcomes more strongly than the legacy or other investigated metrics. Meeting the 45 total MV minutes/week threshold had increased relative risk (RR) for improved/high function (gait speed RR 1.8, 95% confidence interval [95% CI] 1.6, 2.1 and PRO physical function RR 1.4, 95% CI 1.3, 1.6) compared to less active adults. Thresholds were consistent across sex, body mass index, knee osteoarthritis status, and age. Conclusion These results supported a physical activity minimum threshold of 45 total MV minutes/week to promote improved or sustained high function for adults with lower‐extremity joint symptoms. This evidence‐based threshold is less rigorous than federal guidelines (≥150 MV‐bout minutes/week) and provides an intermediate goal towards the federal guideline for adults with lower‐extremity symptoms

Graph Clustering, Variational Image Segmentation Methods and Hough Transform Scale Detection for Object Measurement in Images

© 2016, Springer Science+Business Media New York. We consider the problem of scale detection in images where a region of interest is present together with a measurement tool (e.g. a ruler). For the segmentation part, we focus on the graph-based method presented in Bertozzi and Flenner (Multiscale Model Simul 10(3):1090–1118, 2012) which reinterprets classical continuous Ginzburg–Landau minimisation models in a totally discrete framework. To overcome the numerical difficulties due to the large size of the images considered, we use matrix completion and splitting techniques. The scale on the measurement tool is detected via a Hough transform-based algorithm. The method is then applied to some measurement tasks arising in real-world applications such as zoology, medicine and archaeology

Student conceptions about energy transformations: progression from general chemistry to biochemistry

Students commencing studies in biochemistry must transfer and build on concepts they learned in chemistry and biology classes. It is well established, however, that students have difficulties in transferring critical concepts from general chemistry courses; one key concept is “energy.” Most previous work on students’ conception of energy has focused on their understanding of energy in the context of physics (including the idea of “work”) and/or their understanding of energy in classical physical and inorganic chemistry contexts (particularly Gibbs Free Energy changes, the second law of thermodynamics, and equilibrium under standard conditions within a closed system). For biochemistry, students must go beyond those basic thermodynamics concepts of work, standard energy changes, and closed systems, and instead they must consider what energy flow, use, and transformation mean in living, open, and dynamic systems. In this study we explored students’ concepts about free energy and flow in biological chemical reactions and metabolic pathways by surveys and in-depth interviews. We worked with students in general chemistry classes and biochemistry courses in both an Australian and a US tertiary institution. We address three primary questions (i) What are the most common alternative conceptions held by students when they explain energy-related phenomena in biochemistry?, (ii) What information do students transfer from introductory chemistry and biology when they are asked to consider energy in a biological reaction or reaction pathway?, and (iii) How do students at varying levels of competence articulate their understandings of energy in pathways and biological reactions? The answers to these questions are used to build a preliminary learning progression for understanding “energy” in biochemistry. We also propose crucial elements of content knowledge that instructors could apply to help students better grasp this threshold concept in biochemistry