Telomere length regulation: coupling DNA end processing to feedback regulation of telomerase

The conventional DNA polymerase machinery is unable to fully replicate the ends of linear chromosomes. To surmount this problem, nearly all eukaryotes use the telomerase enzyme, a specialized reverse transcriptase that utizes its own RNA template to add short TG-rich repeats to chromosome ends, thus reversing their gradual erosion occurring at each round of replication. This unique, non-DNA templated mode of telomere replication requires a regulatory mechanism to ensure that telomerase acts at telomeres whose TG tracts are too short, but not at those with long tracts, thus maintaining the protective TG repeat cap at an appropriate average length. The prevailing notion in the field is that telomere length regulation is brought about through a negative feedback mechanism that counts TG repeat-bound protein complexes to generate a signal that regulates telomerase action. This review summarizes experiments leading up to this model and then focuses on more recent experiments, primarily from yeast, that begin to suggest how this counting mechanism might work. The emerging picture is that of a complex interplay between the conventional DNA replication machinery, DNA damage response factors, and a specialized set of proteins that help to recruit and regulate the telomerase enzyme

Enhancing ecosystem services at urban brownfield sites - What value does contaminated soil have in the built environment?

Urban environments are challenged with a plethora of wicked problems in the face of rapid urbanization and land use change, not least natural capital degradation and widespread land and water contamination. Brownfields, under-used sites with real or perceived contamination, are significant urban and peri-urban land resources which, with well-designed remediation and management strategies can address these concerns. Gentle remediation options (GRO) are scalable nature-based techniques which provide significant opportunities for multi-functionality: managing risks posed by contaminants and at the same time enhance ecosystem services (ES) by improving the soil ecosystem in a low-impact, cost-effective manner. GRO align with an increasing interest in taking a holistic view on soil and land management to protect and improve the soil ecosystem for direct human benefit in the form of ES as well as for its indirect, intrinsic value as a haven for biodiversity. This short review aims to present a synthesis of ideas to raise awareness for urban planners about GRO techniques as nature-based solutions which can promote green infrastructure in the urban environment

A risk management framework for Gentle Remediation Options (GRO)

Gentle Remediation Options (GRO) are remediation measures involving plants, fungi, bacteria, and soil amendments that can be applied to manage risks at contaminated sites. Several studies and decision-support tools promote the wider range of benefits provided by GRO, but there is still skepticism regarding GRO implementation. Key issues that need to be better communicated are the various risk mitigation mechanisms, the required risk reduction for an envisioned land use, and the time perspective associated with the risk mitigation mechanisms. To increase the viability and acceptance of GRO, the phytomanagement approach implies the combination of GRO with beneficial green land use, gradually reducing risks and restoring ecosystem services. To strengthen the decision basis for GRO implementation in practice, this paper proposes a framework for risk management and communication of GRO applications to support phytomanagement strategies at contaminated sites. The mapping of the risk mitigation mechanisms is done by an extensive literature review and the Swedish national soil guideline value model is used to derive the most relevant human health exposure pathways and ecological risks for generic green land use scenarios. Results indicate that most of the expected risk mitigation mechanisms are supported by literature, but that knowledge gaps still exist. The framework is demonstrated to support the identification of GRO options for the case study site given two envisioned land uses: biofuel park and allotment garden. A more easily understandable risk management framework, as proposed here, is expected to act as a communication tool to educate decision-makers, regulatory bodies and other stakeholders for better understanding of risk mitigation mechanisms and preliminary timeframes of various GRO, particularly in the early stages of a brownfield redevelopment project

Collaborative Gaze Channelling for Improved Cooperation During Robotic Assisted Surgery

The use of multiple robots for performing complex tasks is becoming a common practice for many robot applications. When different operators are involved, effective cooperation with anticipated manoeuvres is important for seamless, synergistic control of all the end-effectors. In this paper, the concept of Collaborative Gaze Channelling (CGC) is presented for improved control of surgical robots for a shared task. Through eye tracking, the fixations of each operator are monitored and presented in a shared surgical workspace. CGC permits remote or physically separated collaborators to share their intention by visualising the eye gaze of their counterparts, and thus recovers, to a certain extent, the information of mutual intent that we rely upon in a vis-à-vis working setting. In this study, the efficiency of surgical manipulation with and without CGC for controlling a pair of bimanual surgical robots is evaluated by analysing the level of coordination of two independent operators. Fitts' law is used to compare the quality of movement with or without CGC. A total of 40 subjects have been recruited for this study and the results show that the proposed CGC framework exhibits significant improvement (p<0.05) on all the motion indices used for quality assessment. This study demonstrates that visual guidance is an implicit yet effective way of communication during collaborative tasks for robotic surgery. Detailed experimental validation results demonstrate the potential clinical value of the proposed CGC framework. © 2012 Biomedical Engineering Society.link_to_subscribed_fulltex

A global disorder of imprinting in the human female germ line

Imprinted genes are expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin. Correct imprinting is established by germline-specific modifications; failure of this process underlies several inherited human syndromes. All these imprinting control defects are cis-acting, disrupting establishment or maintenance of allele-specific epigenetic modifications across one contiguous segment of the genome. In contrast, we report here an inherited global imprinting defect. This recessive maternal-effect mutation disrupts the specification of imprints at multiple, non-contiguous loci, with the result that genes normally carrying a maternal methylation imprint assume a paternal epigenetic pattern on the maternal allele. The resulting conception is phenotypically indistinguishable from an androgenetic complete hydatidiform mole, in which abnormal extra-embryonic tissue proliferates while development of the embryo is absent or nearly so. This disorder offers a genetic route to the identification of trans-acting oocyte factors that mediate maternal imprint establishment

Differentiating and quantifying carbonaceous (tire, bitumen, and road marking wear) and non-carbonaceous (metals, minerals, and glass beads) non-exhaust particles in road dust samples from a traffic environment

Tires, bitumen, and road markings are important sources of traffic-derived carbonaceous wear particles and microplastic (MP) pollution. In this study, we further developed a machine-learning algorithm coupled to an automated scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) analytical approach to classify and quantify the relative number of the following subclasses contained in environmental road dust: tire wear particles (TWP), bitumen wear particles (BiWP), road markings, reflecting glass beads, metallics, minerals, and biogenic/organics. The method is non-destructive, rapid, repeatable, and enables information about the size, shape, and elemental composition of particles 2–125 μm. The results showed that the method enabled differentiation\ua0between TWP and BiWP for particles &gt; 20 μm with satisfying results. Furthermore, the relative number concentration of the subclasses was similar in both analyzed size fractions (2–20 μm and 20–125 μm), with minerals as the most dominant subclass (2–20 μm x̄ = 78%, 20–125 μm x̄ = 74%) followed by tire and bitumen wear particles, TBiWP, (2–20 μm x̄ = 19%, 20–125 μm x̄ = 22%). Road marking wear, glass beads, and metal wear contributed to x̄ = 1%, x̄ = 0.1%, and x̄ = 1% in the 2–20-μm fraction and to x̄ = 0.5%,x̄ = 0.2%, and x̄ = 0.4% in the 20–125-μm fraction. The present results show that road dust appreciably consists of TWP and BiWP within both the coarse and the fine size fraction. The study delivers quantitative evidence of the importance of tires, bitumen, road marking, and glass beads besides minerals and metals to wear particlesand MP pollution in traffic environments based on environmental (real-world) sample

First-principles derivation of the AdS/CFT Y-systems

We provide a first-principles, perturbative derivation of the AdS5/CFT4 Y-system that has been proposed to solve the spectrum problem of N=4 SYM. The proof relies on the computation of quantum effects in the fusion of some loop operators, namely the transfer matrices. More precisely we show that the leading quantum corrections in the fusion of transfer matrices induce the correct shifts of the spectral parameter in the T-system. As intermediate steps we study UV divergences in line operators up to first order and compute the fusion of line operators up to second order for the pure spinor string in AdS5xS5. We also argue that the derivation can be easily extended to other integrable models, some of which describe string theory on AdS4, AdS3 and AdS2 spacetimes.Comment: 45 pages, 5 figures; v2: minor additions, JHEP versio

Prevention of delirium (POD) for older people in hospital: study protocol for a randomised controlled feasibility trial

Background: Delirium is the most frequent complication among older people following hospitalisation. Delirium may be prevented in about one-third of patients using a multicomponent intervention. However, in the United Kingdom, the National Health Service has no routine delirium prevention care systems. We have developed the Prevention of Delirium Programme, a multicomponent delirium prevention intervention and implementation process. We have successfully carried out a pilot study to test the feasibility and acceptability of implementation of the programme. We are now undertaking preliminary testing of the programme. Methods/Design: The Prevention of Delirium Study is a multicentre, cluster randomised feasibility study designed to explore the potential effectiveness and cost-effectiveness of the Prevention of Delirium Programme. Sixteen elderly care medicine and orthopaedic/trauma wards in eight National Health Service acute hospitals will be randomised to receive the Prevention of Delirium Programme or usual care. Patients will be eligible for the trial if they have been admitted to a participating ward and are aged 65 years or over. The primary objectives of the study are to provide a preliminary estimate of the effectiveness of the Prevention of Delirium Programme as measured by the incidence of new onset delirium, assess the variability of the incidence of new-onset delirium, estimate the intracluster correlation coefficient and likely cluster size, assess barriers to the delivery of the Prevention of Delirium Programme system of care, assess compliance with the Prevention of Delirium Programme system of care, estimate recruitment and follow-up rates, assess the degree of contamination due to between-ward staff movements, and investigate differences in financial costs and benefits between the Prevention of Delirium Programme system of care and standard practice. Secondary objectives are to investigate differences in the number, severity and length of delirium episodes (including persistent delirium); length of stay in hospital; inhospital mortality; destination at discharge; health-related quality of life and health resource use; physical and social independence; anxiety and depression; and patient experience. Discussion: This feasibility study will be used to gather data to inform the design of a future definitive randomised controlled trial. Trial registration: ISRCTN01187372. Registered 13 March 2014