Mushroom body-specific gene regulation by the SWI/SNF chromatin remodeling complex

Over the lifetime of an organism, neurons must establish, remodel, and maintain precise connections in order to form neural circuits that are required for proper nervous system functioning. Disruptions in these processes can lead to neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder. Mutations in genes encoding subunits of the SWI/SNF chromatin remodeling complex have been implicated in ID, yet the role of this complex in neurons is poorly understood. In this project, I established cell-type specific methods to examine the effect of SWI/SNF subunit knockdowns on gene transcription and chromatin structure in the memory-forming neurons of the Drosophila mushroom body (MB) during periods of neuronal remodeling and experience-dependent synaptic plasticity. Combining transcriptome and epigenome profiling of MB neurons at the onset of pupation revealed that the SWI/SNF complex is critical for regulating genes that are essential to MB γ neuron axon pruning during pupation. These genes include the steroid hormone receptor EcR-B1 and members of the ubiquitin proteasome system. Additionally, the SWI/SNF complex was shown to have a stage-specific effect in regulating chromatin accessibility and transcription of genes required during a critical window of experience-dependent synaptic plasticity in juvenile adult flies. Among these were several genes involved in response to stimulus and axon guidance, including: forked end, Calmodulin, and Dichaete, and the gene encoding an actin-binding protein involved in brain development, Ciboulot. This study investigates the neuron-specific gene regulatory role of the SWI/SNF complex. These findings reveal specific roles for the SWI/SNF complex in regulating distinct processes in post-mitotic neurons and provide the groundwork in understanding the effect of chromatin regulation in SWI/SNF-related ID

Tidal capture of stars by supermassive black holes: implications for periodic nuclear transients and quasi-periodic eruptions

Stars that plunge into the centre of a galaxy are tidally perturbed by a supermassive black hole (SMBH), with closer encounters resulting in larger perturbations. Exciting these tides comes at the expense of the star’s orbital energy, which leads to the naive conclusion that a smaller pericentre (i.e. a closer encounter between the star and SMBH) always yields a more tightly bound star to the SMBH. However, once the pericentre distance is small enough that the star is partially disrupted, morphological asymmetries in the mass lost by the star can yield an increase in the orbital energy of the surviving core, resulting in its ejection – not capture – by the SMBH. Using smoothed particle hydrodynamics simulations, we show that the combination of these two effects – tidal excitation and asymmetric mass-loss – results in a maximum amount of energy lost through tides of ∼2.5 per cent of the binding energy of the star, which is significantly smaller than the theoretical maximum of the total stellar binding energy. This result implies that stars that are repeatedly partially disrupted by SMBHs many (≳10) times on short-period orbits (≲few years), as has been invoked to explain the periodic nuclear transient ASASSN-14ko and quasi-periodic eruptions, must be bound to the SMBH through a mechanism other than tidal capture, such as a dynamical exchange (i.e. Hills capture)

Accidental Ingestion of an Implant Screwdriver: A Case Report and Literature Review.

Head and neck oncology patients are high risk for ingestion or aspiration of dental instruments during treatment, due to altered anatomy and sensation. This article describes a case report of accidental ingestion of an implant screwdriver during the prosthetic phase of oral rehabilitation of a 79 year old oncology patient. The management protocol is described which included referral to the medical Accident and Emergency department, where the object was safely removed from the stomach via endoscopy. A review of similar cases of ingestion/inhalation in the literature suggests implant screwdrivers should be retrieved as safe passage through the gastrointestinal system is not assured. Awareness of the medical history and risk factors should alert clinicians to be extra cautious, and preventative strategies should be implemented at all times. Preventative measures include ligation of instruments with floss/suture material, treatment in a more vertical position, and use of rubber dam where possible

The Agewell trial: a pilot randomised controlled trial of a behaviour change intervention to promote healthy ageing and reduce risk of dementia in later life.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Lifestyle factors represent prime targets for behaviour change interventions to promote healthy ageing and reduce dementia risk. We evaluated a goal-setting intervention aimed at promoting increased cognitive and physical activity and improving mental and physical fitness, diet and health. METHODS: This was a pilot randomised controlled trial designed to guide planning for a larger-scale investigation, provide preliminary evidence regarding efficacy, and explore feasibility and acceptability. Primary outcomes were engagement in physical and cognitive activity. Participants aged over 50 living independently in the community were recruited through a community Agewell Centre. Following baseline assessment participants were randomly allocated to one of three conditions: control (IC) had an interview in which information about activities and health was discussed; goal-setting (GS n = 24) had an interview in which they set behaviour change goals relating to physical, cognitive and social activity, health and nutrition; and goal-setting with mentoring (GM, n = 24) had the goal-setting interview followed by bi-monthly telephone mentoring. Participants and researchers were blinded to group assignment. Participants were reassessed after 12 months. RESULTS: Seventy-five participants were randomised (IC n = 27, GS n = 24, GM n = 24). At 12-month follow-up, the two goal-setting groups, taken together (GS n = 21, GM n = 22), increased their level of physical (effect size 0.37) and cognitive (effect size 0.15) activity relative to controls (IC n = 27). In secondary outcomes, the two goal-setting groups taken together achieved additional benefits compared to control (effect sizes ≥ 0.2) in memory, executive function, cholesterol level, aerobic capacity, flexibility, balance, grip strength, and agility. Adding follow-up mentoring produced further benefits compared to goal-setting alone (effect sizes ≥ 0.2) in physical activity, body composition, global cognition and memory, but not in other domains. Implementation of the recruitment procedure, assessment and intervention was found to be feasible and the approach taken was acceptable to participants, with no adverse effects. CONCLUSIONS: A brief, low-cost goal-setting intervention is feasible and acceptable, and has the potential to achieve increased activity engagement. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30080637.This trial was funded by Medical Research Council grant G1001888/1 to LC, JVH, IRJ, JT and CJW. The funding body played no role in the design of the study, in collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. We acknowledge the support of Age Cymru Gwynedd a Môn including John Clifford Jones, Maldwyn Roberts, Stephen Williams and Mici Plwm. We would like to thank Sharman Harris and Catrin Searell, Department of Clinical Chemistry, Ysbyty Gwynedd, Bangor, the volunteers at the Nefyn Agewell Centre, and all the members of the Nefyn Agewell Centre, and especially all those who took part in the research project. We are grateful to Professor Carol Brayne, Cambridge University, Professor Martin Knapp, London School of Economics, Professor Mike Martin, Zürich University, and Professor Robin Morris, King’s College London Institute of Psychiatry, who acted as external advisors to the project. Special thanks go to Andrew Brand for statistical advice

Electricity generation from digitally printed cyanobacteria

Microbial biophotovoltaic cells exploit the ability of cyanobacteria and microalgae to convert light energy into electrical current using water as the source of electrons. Such bioelectrochemical systems have a clear advantage over more conventional microbial fuel cells which require the input of organic carbon for microbial growth. However, innovative approaches are needed to address scale-up issues associated with the fabrication of the inorganic (electrodes) and biological (microbe) parts of the biophotovoltaic device. Here we demonstrate the feasibility of using a simple commercial inkjet printer to fabricate a thin-film paper-based biophotovoltaic cell consisting of a layer of cyanobacterial cells on top of a carbon nanotube conducting surface. We show that these printed cyanobacteria are capable of generating a sustained electrical current both in the dark (as a ‘solar bio-battery’) and in response to light (as a ‘bio-solar-panel’) with potential applications in low-power devices.The authors are grateful for funding provided by the UK Engineering and Physical Sciences Research Council (EPSRC), EnAlgae (http://www.enalgae.eu/, INTERREG IVB NWE) the Shuttleworth Foundation, and the Leverhulme Trust

The effect of high dose antibiotic impregnated cement on rate of surgical site infection after hip hemiarthroplasty for fractured neck of femur : a protocol for a double-blind quasi randomised controlled trial

Background: Mortality following hip hemiarthroplasty is in the range of 10-40% in the first year, with much attributed to post-operative complications. One such complication is surgical site infection (SSI), which at the start of this trial affected 4.68% of patients in the UK having this operation. Compared to SSI rates of elective hip surgery, at less than 1%, this figure is elevated. The aim of this quasi randomised controlled trial (RCT) is to determine if high dose antibiotic impregnated cement can reduce the SSI in patients at 12-months after hemiarthroplasty for intracapsular fractured neck of femur. Methods: 848 patients with an intracapsular fractured neck of femur requiring a hip hemiarthroplasty are been recruited into this two-centre double-blind quasi RCT. Participants were recruited before surgery and quasi randomised to standard care or intervention group. Participants, statistician and outcome assessors were blind to treatment allocation throughout the study. The intervention consisted of high dose antibiotic impregnated cement consisting of 1 gram Clindamycin and 1 gram of Gentamicin. The primary outcome is Health Protection Agency (HPA) defined deep surgical site infection at 12 months. Secondary outcomes include HPA defined superficial surgical site infection at 30 days, 30 and 90-day mortality, length of hospital stay, critical care stay, and complications. Discussion: Large randomised controlled trials assessing the effectiveness of a surgical intervention are uncommon, particularly in the speciality of orthopaedics. The results from this trial will inform evidence-based recommendations for antibiotic impregnated cement in the management of patients with a fractured neck of femur undergoing a hip hemiarthroplasty. If high dose antibiotic impregnated cement is found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip hemiarthroplasty

Description of Immature Stages and Life Cycle of the Treehopper, Guayaquila projecta

Immature stages of the membracid Guayaquila projecta (Funkhouser) (Hemiptera: Cicadomorpha: Membracidae), collected in San Salvador de Jujuy, Argentina on Bougainvillea glabra Choisy (Caryophyllales: Nyctaginaceae), are described in detail based on specimens reared in the laboratory. Like other membracids, this species has five nymphal instars, not seven as previously reported. Morphological characters for identifying the different instars of G. projecta, determining the sex of later instars and distinguishing this species from other members of the Guayaquila pugnax group, are discussed. At 19 ±± 4°°C, RH 59 ±± 9%, and a 12:12 L:D photoperiod, the time required for development from egg to adult emergence was 73 ±± 5 days

Living with frailty and haemodialysis: a qualitative study

Background: Frailty is highly prevalent in people receiving haemodialysis (HD) and is associated with poor outcomes. Understanding the lived experiences of this group is essential to inform holistic care delivery. / Methods: Semi-structured interviews with N = 25 prevalent adults receiving HD from 3 HD units in the UK. Eligibility criteria included a Clinical Frailty Scale (CFS) score of 4–7 and a history of at least one fall in the last 6 months. Sampling began guided by maximum variation sampling to ensure diversity in frailty status; subsequently theoretical sampling enabled exploration of preliminary themes. Analysis was informed by constructivist grounded theory; later we drew upon the socioecological model. / Results: Participants had a mean age of 69 ± 10 years, 13 were female, and 13 were White British. 14 participants were vulnerable or mildly frail (CFS 4–5), and 11 moderately or severely frail (CFS 6–7). Participants characterised frailty as weight loss, weakness, exhaustion, pain and sleep disturbance arising from multiple long-term conditions. Participants’ accounts revealed: the consequences of frailty (variable function and psychological ill-health at the individual level; increasing reliance upon family at the interpersonal level; burdensome health and social care interactions at the organisational level; reduced participation at the community level; challenges with financial support at the societal level); coping strategies (avoidance, vigilance, and resignation); and unmet needs (overprotection from family and healthcare professionals, transactional health and social care exchanges). / Conclusions: The implementation of a holistic needs assessment, person-centred health and social care systems, greater family support and enhancing opportunities for community participation may all improve outcomes and experience. An approach which encompasses all these strategies, together with wider public health interventions, may have a greater sustained impact. Trial registration: ISRCTN12840463

Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices in the peripheral ER

The endoplasmic reticulum (ER) is an expansive, membrane-enclosed organelle that plays crucial roles in numerous cellular functions. We used emerging superresolution imaging technologies to clarify the morphology and dynamics of the peripheral ER, which contacts and modulates most other intracellular organelles. Peripheral components of the ER have classically been described as comprising both tubules and flat sheets. We show that this system consists almost exclusively of tubules at varying densities, including structures that we term ER matrices. Conventional optical imaging technologies had led to misidentification of these structures as sheets because of the dense clustering of tubular junctions and a previously uncharacterized rapid form of ER motion. The existence of ER matrices explains previous confounding evidence that had indicated the occurrence of ER "sheet" proliferation after overexpression of tubular junction-forming proteins

Monthly quasi-periodic eruptions from repeated stellar disruption by a massive black hole

In recent years, searches of archival X-ray data have revealed galaxies exhibiting nuclear quasi-periodic eruptions with periods of several hours. These are reminiscent of the tidal disruption of a star by a supermassive black hole. The repeated, partial stripping of a white dwarf in an eccentric orbit around an ~105 M⊙ black hole provides an attractive model. A separate class of periodic nuclear transients, with much longer timescales, have recently been discovered optically and may arise from the partial stripping of a main-sequence star by an ~107 M⊙ black hole. No clear connection between these classes has been made. We present the discovery of an X-ray nuclear transient that shows quasi-periodic outbursts with a period of weeks. We discuss possible origins for the emission and propose that this system bridges the two existing classes outlined above. This discovery was made possible by the rapid identification, dissemination and follow-up of an X-ray transient found by the new live Swift-XRT transient detector, demonstrating the importance of low-latency, sensitive searches for X-ray transients