57,476 Works

Modification of a Constitutive to Glucose-Responsive Liver-Specific Promoter Resulted in Increased Efficacy of Adeno-Associated Virus Serotype 8-Insulin Gene Therapy of Diabetic Mice

Kian Chuan Sia, Zhen Ying Fu, Roy Y. Calne, Amit C. Nathwani, Kok Onn Lee & Shu Uin Gan
We have previously used a hepatotropic adeno-associated viral (AAV) vector with a modified human insulin gene to treat diabetic mice. The HLP (hybrid liver-specific promoter) used was constitutively active and non-responsive to glucose. In this study, we examined the effects of addition of glucose responsive elements (R3G) and incorporation of a 3′ albumin enhancer (3′iALB) on insulin expression. In comparison with the original promoter, glucose responsiveness was only observed in the modified promoters in vitro...

Modelling Day-to-Day Variability of Glucose-Insulin Regulation over 12-Week Home Use of Closed-loop Insulin Delivery

Yue Ruan, Malgorzata Wilinska, Hood Thabit & Roman Hovorka
Parameters of physiological models of glucose-insulin regulation in type 1 diabetes have previously been estimated using data collected over short periods of time and lack the quantification of day-to-day variability. We developed a new hierarchical model to relate subcutaneous insulin delivery and carbohydrate intake to continuous glucose monitoring over 12 weeks while describing day-to-day variability. Sensor glucose data sampled every 10 min, insulin aspart delivery and meal intake were analyzed from 8 adults with type...

Near-wall diffusion tensor of an axisymmetric colloidal particle

Maciej Lisicki, B Cichocki & E Wajnryb
Hydrodynamic interactions with confining boundaries often lead to drastic changes in the diffusive behaviour of microparticles in suspensions. For axially symmetric particles, earlier numerical studies have suggested a simple form of the near-wall diffusion matrix which depends on the distance and orientation of the particle with respect to the wall, which is usually calculated numerically. In this work, we derive explicit analytical formulae for the dominant correction to the bulk diffusion tensor of an axially...

Research data supporting Farmer, Baron-Cohen, & Skylark \"People with autism spectrum conditions make more consistent decisions\"

George Farmer & William Skylark
The data comprise responses to individual difference measures of cognitive ability and autistic traits, and to a decsion-making task in which people make a series of choices between consumer products. A description of the files is included in the accompanying readme.txt file, and full details of the tasks and data collection procedures are given in the associated publication.

Wrist Accelerometer Cut Points for Classifying Sedentary Behavior in Children.

Loo Christiana MT VAN, Anthony D Okely, Marijka J Batterham, Trina Hinkley, Ulf Ekelund, Soren Brage, John J Reilly, Stewart G Trost, Rachel A Jones, Xanne Janssen & Dylan P Cliff
INTRODUCTION: To examine the validity and accuracy of wrist accelerometers for classifying sedentary behavior (SB) in children. METHODS: Fifty-seven children (5-8y and 9-12y) completed a ~170min protocol including 15 semi-structured activities and transitions. Nine ActiGraph (GT3X+) and two GENEActiv wrist cut-points were evaluated. Direct observation was the criterion measure. The accuracy of wrist cut-points was compared to that achieved by the ActiGraph hip cut-point (≤25 counts/15s) and the thigh-mounted activPAL3. Analyses included equivalence testing, Bland-Altman...

Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma.

Martin Köbel, Anna M Piskorz, Sandra Lee, Shuhong Lui, Cecile LePage, Francesco Marass, Nitzan Rosenfeld, Anne-Marie Mes Masson & James Brenton
TP53 mutations are ubiquitous in high-grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low-grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has not been established. The objective of this study was to test whether improved methods for p53 IHC could reliably predict TP53 mutations independently identified...

Effects of fasting on serial measurements of hyperpolarized [1-$^{13}$C]pyruvate metabolism in tumors

Eva M Serrao, Tiago B Rodrigues, Ferdia Gallagher, Mikko I Kettunen, Brett WC Kennedy, Sarah L Vowler, Keith A Burling & Kevin Brindle
Imaging the metabolism of hyperpolarized [1-$^{13}$C]pyruvate has shown considerable promise in preclinical studies in oncology, particularly for assessment of early treatment response. The repeatability of measurements of $^{13}$C label exchange between pyruvate and lactate were determined in a murine lymphoma model in fasted and non-fasted animals. The fasted state showed lower intra-individual variability, although the [1-$^{13}$C]Lac/[1-$^{13}$C]Pyr signal ratio was significantly higher in fasted mice when compared to non-fasted mice, which may be explained by higher...

More medicines alone cannot ensure the treatment of neglected tropical diseases.

Goylette Chami & Donald AP Bundy
Neglected tropical diseases afflict more than one billion of the world’s poorest people. Annual pharmaceutical donations of billions of preventive chemotherapies for neglected tropical diseases enable the largest en masse treatment campaigns globally with respect to the number of people targeted for treatment. However, the blanket distribution of medicines at no cost to individuals in need of treatment does not guarantee that those individuals are treated. Here we argue that the expansion of medicine donations...

Identification of a regeneration-organizing cell in the Xenopus tail

Can Aztekin, Thomas Hiscock, John Marioni, John Gurdon, Benjamin Simons & Jerome Jullien
Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential. To characterize this regenerative response, we performed single-cell RNA sequencing (scRNA-seq) following tail amputation. By comparing naturally-occurring regeneration-competent and incompetent tadpoles, we identified a previously unrecognized cell type that we term the regeneration-organizing cell (ROC). ROCs are present in the epidermis during normal tail development, and specifically relocalize to the amputation plane of regeneration-competent tadpoles, forming the wound epidermis. Genetic ablation or manual removal of...

Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche.

Yu Kitadate, David J Jörg, Moe Tokue, Ayumi Maruyama, Rie Ichikawa, Soken Tsuchiya, Eri Segi-Nishida, Toshinori Nakagawa, Aya Uchida, Chiharu Kimura-Yoshida, Seiya Mizuno, Fumihiro Sugiyama, Takuya Azami, Masatsugu Ema, Chiyo Noda, Satoru Kobayashi, Isao Matsuo, Yoshiakira Kanai, Takashi Nagasawa, Yukihiko Sugimoto, Satoru Takahashi, Benjamin Simons & Shosei Yoshida
In many tissues, homeostasis is maintained by physical contact between stem cells and an anatomically-defined niche. However, how stem cell homeostasis is achieved in environments where cells are motile and dispersed among their progeny remains unknown. Using murine spermatogenesis as a model, we find that spermatogenic stem cell density is tightly regulated by the supply of fibroblast growth factors (FGFs) from lymphatic endothelial cells. We propose that stem cell homeostasis is achieved through competition for...

Identifying key targets for interventions to improve psychological wellbeing: replicable results from four UK cohorts.

Jan Stochl, Emma Soneson, AP Wagner, Golam Khandaker, Ian Goodyer & Peter Jones
Background An increasing importance is being placed on mental health and wellbeing at individual and population levels. While there are several interventions that have been proposed to improve wellbeing, more evidence is needed to understand which aspects of wellbeing are most influential. This study aimed to identify key items that signal improvement of mental health and wellbeing. Methods Using network analysis, we identified the most central items in the graph network estimated from the well-established...

The role of dopamine in the brain - lessons learned from Parkinson's disease.

David Meder, Damian Marc Herz, James Rowe, Stéphane Lehéricy & Hartwig Roman Siebner

Analytical validation of a next generation sequencing liquid biopsy assay for high sensitivity broad molecular profiling.

Vincent Plagnol, Samuel Woodhouse, Karen Howarth, Stefanie Lensing, Matt Smith, Michael Epstein, Mikidache Madi, Sarah Smalley, Catherine Leroy, Jonathan Hinton, Frank De Kievit, Esther Musgrave-Brown, Colin Herd, Katherine Baker-Neblett, Will Brennan, Peter Dimitrov, Nathan Campbell, Clive Morris, Nitzan Rosenfeld, James Clark, Davina Gale, Jamie Platt, John Calaway, Greg Jones & Tim Forshew

Defining the clonal dynamics leading to mouse skin tumour initiation

Adriana Sánchez-Danés, Edouard Hannezo, Jean-Christophe Larsimont, Mélanie Liagre, Khalil Kass Youssef, Benjamin Simons & Cédric Blanpain
The changes that occur in cell dynamics following oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the impact of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, were competent to initiate tumour formation upon oncogenic hedgehog signalling. Interestingly, this difference...

Treatment attributes for Uganda Village Networks 2013

Goylette Chami
This anonymized data is an addition to the following anonymized social network dataset. https://doi.org/10.17863/CAM.15616 Project: Social network analysis for improving mass drug administration. Data collection: Census-based, observational survey. Household level treatment outcomes are provided. 'Treatment_offer.txt' provides a binary variable of the household's treatment offer status for all households included in friendship networks. Treatment offer is positive if at least one eligible person in the household was offered treatment. See the following publication and its supplementary...

Neuroticism predicts the impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex.

Bettina Hornboll, Julian Macoveanu, Ayna Nejad, James Rowe, Rebecca Elliott, Gitte M Knudsen, Hartwig R Siebner & Olaf B Paulson
The personality trait neuroticism is associated with increased vulnerability to anxiety and mood disorders, conditions linked with abnormal serotonin neurotransmission and emotional processing. The interaction between neuroticism and serotonin during emotional processing is however not understood. Here we investigate how individual neuroticism scores influence the neural response to negative emotional faces and their sensitivity to serotonergic tone. Twenty healthy participants performed an emotional face task under functional MRI on three occasions: increased serotonin tone following...

Effects of Collection and Processing Procedures on Plasma Circulating Cell-Free DNA from Cancer Patients.

Bente Risberg, Dana WY Tsui, Heather Biggs, Andrea Ruiz-Valdepenas Martin De Almagro, Sarah-Jane Dawson, Charlotte Hodgkin, Linda Jones, Christine Parkinson, Anna Piskorz, Francesco Marass, Sandunie Chandrananda, Elizabeth Moore, James Morris, Vincent Plagnol, Nitzan Rosenfeld, Carlos Caldas, James Brenton & Davina Gale
Circulating tumour DNA (ctDNA) offers new opportunities for non-invasive cancer management. Detecting ctDNA in plasma is challenging since it constitutes only a minor fraction of the total cell-free DNA (cfDNA). Pre-analytical factors affect cfDNA levels contributed from leukocyte lysis, hence the ability to detect low-frequency mutant alleles. This study investigates the effects of (i) delay in processing (ii) storage temperatures, (iii) different blood collection tubes, (iv) centrifugation protocols and (v) sample shipment on cfDNA levels....

Branch-recombinant Gaussian processes for analysis of perturbations in biological time series.

Christopher A Penfold, Anastasiya Sybirna, John Reid, Yun Huang, Lorenz Wernisch, Zoubin Ghahramani, Murray Grant & Azim Surani

BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment.

Giuseppina D'Alessandro, Donna Rose Whelan, Sean Michael Howard, Valerio Vitelli, Xavier Renaudin, Marek Adamowicz, Fabio Iannelli, Corey Winston Jones-Weinert, MiYoung Lee, Valentina Matti, Wei Ting C Lee, Michael John Morten, Ashok Venkitaraman, Petr Cejka, Eli Rothenberg & Fabrizio D'Adda Di Fagagna
DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase...

GABA-ergic Dynamics in Human Frontotemporal Networks Confirmed by Pharmaco-Magnetoencephalography.

Natalie Adams, Laura Hughes, Holly N Phillips, Alexander D Shaw, Alexander Murley, David Nesbitt, Thomas Cope, W Richard Bevan-Jones, Luca Passamonti & James Rowe
To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, as generative models of magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked ‘mismatch negativity’ response and transiently induced oscillations. Here, we...

Data for the manuscript entitled \"Associations between Bacterial Infections and Blood Pressure in Pregnancy\"

Clive Petry, Kenneth Ong, IA Hughes, Carlo Acerini & David Dunger
Data for the paper published in Pregnancy Hypertension entitled "Associations between Bacterial Infections and Blood Pressure in Pregnancy" (doi 10.1016/j.preghy.2017.09.004)

Influence of the Vibrational Modes from the Organic Moieties in 2D Lead Halides on Excitonic Recombination and Phase Transition

RF Moral, JC Germino, LG Bonato, DB Almeida, EM Therézio, TDZ Atvars, Samuel Stranks, RA Nome & AF Nogueira

Combinatorial expression of GPCR isoforms affects signalling and drug responses.

Maria Marti-Solano, Stephanie E Crilly, Duccio Malinverni, Christian Munk, Matthew Harris, Abigail Pearce, Tezz Quon, Amanda E Mackenzie, Xusheng Wang, Junmin Peng, Andrew B Tobin, Graham Ladds, Graeme Milligan, David E Gloriam, Manojkumar A Puthenveedu & M Madan Babu

Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences.

Darren Price, Lorraine Tyler, R Neto Henriques, KL Campbell, N Williams, MS Treder, Taylor, Cam-CAN & Rik Henson

Compositional characterization of Etruscan earthen architecture and ceramic production

L Ceccarelli, C Moletti, M Bellotto, G Dotelli & Simon Stoddart
The purpose of this paper is to present the results of new research into Etruscan technology for earthen architecture as well as ceramic production in the upper Tiber valley in Central Italy, using as case-study the Etruscan settlement of Col di Marzo (Perugia). The study aims to determine the compositional differences of the raw material employed as building material and for ceramic production by XRD, TG-DTG, FTIR and geotechnical analyses. The research also advances the...

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