Obsessive compulsive disorder in children and young people : experiences of children with OCD and the involvement of families in treatment

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Drosophila mRNA Localization During Later Development: Past, Present, and Future

Multiple mechanisms tightly regulate mRNAs during their transcription, translation, and degradation. Of these, the physical localization of mRNAs to specific cytoplasmic regions is relatively easy to detect; however, linking localization to functional regulatory roles has been more difficult to establish. Historically, Drosophila melanogaster is a highly effective model to identify localized mRNAs and has helped identify roles for this process by regulating various cell activities. The majority of the well-characterized functional roles for localizing mRNAs to sub-regions of the cytoplasm have come from the Drosophila oocyte and early syncytial embryo. At present, relatively few functional roles have been established for mRNA localization within the relatively smaller, differentiated somatic cell lineages characteristic of later development, beginning with the cellular blastoderm, and the multiple cell lineages that make up the gastrulating embryo, larva, and adult. This review is divided into three parts—the first outlines past evidence for cytoplasmic mRNA localization affecting aspects of cellular activity post-blastoderm development in Drosophila. The majority of these known examples come from highly polarized cell lineages such as differentiating neurons. The second part considers the present state of affairs where we now know that many, if not most mRNAs are localized to discrete cytoplasmic regions in one or more somatic cell lineages of cellularized embryos, larvae or adults. Assuming that the phenomenon of cytoplasmic mRNA localization represents an underlying functional activity, and correlation with the encoded proteins suggests that mRNA localization is involved in far more than neuronal differentiation. Thus, it seems highly likely that past-identified examples represent only a small fraction of localization-based mRNA regulation in somatic cells. The last part highlights recent technological advances that now provide an opportunity for probing the role of mRNA localization in Drosophila, moving beyond cataloging the diversity of localized mRNAs to a similar understanding of how localization affects mRNA activity

Symplectic geometry and circuit quantization

Circuit quantization is an extraordinarily successful theory that describes the behavior of quantum circuits with high precision. The most widely used approach of circuit quantization relies on introducing a classical Lagrangian whose degrees of freedom are either magnetic fluxes or electric charges in the circuit. By combining nonlinear circuit elements (such as Josephson junctions or quantum phase slips), it is possible to build circuits where a standard Lagrangian description (and thus the standard quantization method) does not exist. Inspired by the mathematics of symplectic geometry and graph theory, we address this challenge, and present a Hamiltonian formulation of non-dissipative electrodynamic circuits. The resulting procedure for circuit quantization is independent of whether circuit elements are linear or nonlinear, or if the circuit is driven by external biases. We explain how to re-derive known results from our formalism, and provide an efficient algorithm for quantizing circuits, including those that cannot be quantized using existing methods.Comment: 30 pages, 8 figure

ACTIVE: a randomised feasibility trial of a behavioural intervention to reduce fatigue in women undergoing radiotherapy for early breast cancer: study protocol

Background Fatigue is rated as the most distressing side effect of radiotherapy treatment for curable breast cancer. About four in ten women treated experience fatigue, which can last for years after treatment. The impact of this debilitating tiredness is loss of independence and impaired physical and mental function. Our study will take a behavioural intervention with demonstrated effect in treating fatigue in a mixed group of chemotherapy patients and adapt it for women undergoing radiotherapy for early breast cancer. The purpose of this trial is to evaluate the feasibility of delivering the intervention in the radiotherapy pathway for patients at a high risk of fatigue and to explore participants’ experiences of the trial and intervention. Methods A pragmatic single-site non-blinded feasibility trial of a behavioural intervention. Main inclusion criteria are prescription of the UK standard 40 Gy in 15 fractions over 3 weeks of radiotherapy (± tumour bed boost) for early (stage 0–IIIa) breast cancer. The total projected sample size after attrition is 70. A previously developed fatigue risk score tool will be used to predict individual’s likelihood of experiencing fatigue. Thirty women predicted to be at a high risk of experiencing significant fatigue will be allocated in the ratio 2:1 to the behavioural intervention or education trial arms, respectively. These feasibility trial participants will be assessed at baseline, after 10 and 15 fractions of radiotherapy and 10 days, 3 weeks and 6 months after radiotherapy. A further 40 women predicted to be at a lower risk of fatigue will join a risk score validation group. Measures to assess feasibility include recruitment, retention and completion rates and variation in implementation of the intervention. Process evaluation with intervention providers and users includes fidelity and adherence checks and qualitative interviews to understand how changes in behaviour are initiated and sustained. Discussion This feasibility study collates data to both inform the progression to and design of a future definitive trial and to refine the intervention

Marine Noise Pollution - Increasing Recognition But Need for More Practical Action

Over the last two decades, marine noise pollution has become increasingly recognized as an issue of major significance. The issue has become a primary focus of marine mammal research, but is also of concern to the public and policy makers. The result has been efforts involving a variety of disciplines, and relevant legislation and associated guidance are now in place in many parts of the world. Most current mitigation efforts are directed at reducing the risk of injury from exposure to intense noise, although the effectiveness of such mitigation measures in terms of risk reduction has rarely been quantified. Longer-term chronic impacts of noise including disturbance or masking of sounds critical for feeding and reproduction have received substantially less attention in management. New technologies are being developed for a number of activities which can substantially reduce noise inputs into the marine environment. As with other forms of pollution, reducing input at source is likely to be the most effective way of reducing impacts. We recommend as a priority the implementation of noise quieting technologies and the spatial and temporal exclusion of noise to minimize contact with marine life

Gawky is a component of cytoplasmic mRNA processing bodies required for early Drosophila development

In mammalian cells, the GW182 protein localizes to cytoplasmic bodies implicated in the regulation of messenger RNA (mRNA) stability, translation, and the RNA interference pathway. Many of these functions have also been assigned to analogous yeast cytoplasmic mRNA processing bodies. We have characterized the single Drosophila melanogaster homologue of the human GW182 protein family, which we have named Gawky (GW). Drosophila GW localizes to punctate, cytoplasmic foci in an RNA-dependent manner. Drosophila GW bodies (GWBs) appear to function analogously to human GWBs, as human GW182 colocalizes with GW when expressed in Drosophila cells. The RNA-induced silencing complex component Argonaute2 and orthologues of LSm4 and Xrn1 (Pacman) associated with 5′–3′ mRNA degradation localize to some GWBs. Reducing GW activity by mutation or antibody injection during syncytial embryo development leads to abnormal nuclear divisions, demonstrating an early requirement for GWB-mediated cytoplasmic mRNA regulation. This suggests that gw represents a previously unknown member of a small group of genes that need to be expressed zygotically during early embryo development

Seasonal dynamics of the wild rodent faecal virome

Viral discovery studies in wild animals often rely on cross-sectional surveys at a single time point. As a result, our understanding of the temporal stability of wild animal viromes remains poorly resolved. While studies of single host–virus systems indicate that host and environmental factors influence seasonal virus transmission dynamics, comparable insights for whole viral communities in multiple hosts are lacking. Utilizing noninvasive faecal samples from a long-term wild rodent study, we characterized viral communities of three common European rodent species (Apodemus sylvaticus, A. flavicollis and Myodes glareolus) living in temperate woodland over a single year. Our findings indicate that a substantial fraction of the rodent virome is seasonally transient and associated with vertebrate or bacteria hosts. Further analyses of one of the most common virus families, Picornaviridae, show pronounced temporal changes in viral richness and evenness, which were associated with concurrent and up to ~3-month lags in host density, ambient temperature, rainfall and humidity, suggesting complex feedbacks from the host and environmental factors on virus transmission and shedding in seasonal habitats. Overall, this study emphasizes the importance of understanding the seasonal dynamics of wild animal viromes in order to better predict and mitigate zoonotic risks