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Wellcome Open Research

Thomas L Williams, Alexander R Nödling, Yu-Hsuan Tsai, Louis Y P Luk
Background: Identification of organocatalysts functioning in aqueous environments will provide methods for more sustainable chemical transformations and allow tandem reactions with biocatalysts, like enzymes. Here we examine three water-soluble carbapenem antibiotics (meropenem, doripenem, and ertapenem) as secondary amine organocatalysts in aqueous environments. Methods: The Michael addition of nitromethane to cinnamaldehyde was used as the model reaction. The reactions were monitored by 1 H NMR, and the enantioselectivity was determined by chiral HPLC...
2018: Wellcome Open Research
Jean Golding, Yasmin Iles-Caven, Genette Ellis, Steven Gregory, Stephen Nowicki
Background: The concept of locus of control of reinforcement was introduced by Julian Rotter and has been the focus of intense research for nearly half a century.  Surprisingly little research has been directed at clarifying antecedents of locus of control (LOC) orientations in adult men apart from a few small studies. We previously identified a number of independent antecedents associated with women's LOC, including features of their parents and early childhood. This raised the question as to whether these factors were also associated with the development of LOC in men...
2018: Wellcome Open Research
Joseph Donovan, Nguyen Hoan Phu, Le Thi Phuong Thao, Nguyen Huu Lan, Nguyen Thi Hoang Mai, Nguyen Thi Mai Trang, Nguyen Thi Thu Hiep, Tran Bao Nhu, Bui Thi Bich Hanh, Vu Thi Phuong Mai, Nguyen Duc Bang, Do Chau Giang, Dang Thi Minh Ha, Jeremy Day, Nguyen Tt Thuong, Nguyen Nang Vien, Ronald B Geskus, Tran Tinh Hien, Evelyne Kestelyn, Marcel Wolbers, Nguyen Van Vinh Chau, Guy E Thwaites
Background:  Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H), predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected individuals. The primary aim of this study is to determine whether LTA4H genotype determines benefit or harm from adjunctive dexamethasone in HIV-uninfected Vietnamese adults with TBM. The secondary aim is to investigate alternative management strategies in individuals who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy...
2018: Wellcome Open Research
Laura J A Hardwick, Anna Philpott
The proneural basic-helix-loop-helix (bHLH) transcription factor Ascl1 is a master regulator of neurogenesis in both central and peripheral nervous systems in vivo, and is a central driver of neuronal reprogramming in vitro . Over the last three decades, assaying primary neuron formation in Xenopus embryos in response to transcription factor overexpression has contributed to our understanding of the roles and regulation of proneural proteins like Ascl1, with homologues from different species usually exhibiting similar functional effects...
2018: Wellcome Open Research
Alvina G Lai, Donall Forde, Wai Hoong Chang, Fang Yuan, Xiaodong Zhuang, Claudia Orbegozo Rubio, Chun-Xiao Song, Jane A McKeating
Background: Little is known about the impact of nutrients on cellular transcriptional responses, especially in face of environmental stressors such as oxygen deprivation. Hypoxia-inducible factors (HIF) coordinate the expression of genes essential for adaptation to oxygen-deprived environments. A second family of oxygen-sensing genes known as the alpha-ketoglutarate-dependent dioxygenases are also implicated in oxygen homeostasis and epigenetic regulation. The relationship between nutritional status and cellular response to hypoxia is understudied...
2018: Wellcome Open Research
Keith A Jolley, James E Bray, Martin C J Maiden
The website hosts a collection of open-access, curated databases that integrate population sequence data with provenance and phenotype information for over 100 different microbial species and genera.  Although the PubMLST website was conceived as part of the development of the first multi-locus sequence typing (MLST) scheme in 1998 the software it uses, the Bacterial Isolate Genome Sequence database (BIGSdb, published in 2010), enables PubMLST to include all levels of sequence data, from single gene sequences up to and including complete, finished genomes...
2018: Wellcome Open Research
Clive J Petry, Ken K Ong, Keith A Burling, Peter Barker, Sandra F Goodburn, John R B Perry, Carlo L Acerini, Ieuan A Hughes, Rebecca C Painter, Gijs B Afink, David B Dunger, Stephen O'Rahilly
Background: Although nausea and vomiting are very common in pregnancy, their pathogenesis is poorly understood. We tested the hypothesis that circulating growth and differentiation factor 15 (GDF15) concentrations in early pregnancy, whose gene is implicated in hyperemesis gravidarum, are associated with nausea and vomiting. Methods: Blood samples for the measurement of GDF15 and human chorionic gonadotrophin (hCG) concentrations were obtained early in the second trimester (median 15.1 (interquartile range 14...
2018: Wellcome Open Research
Adhish Walvekar, Zeenat Rashida, Hemanth Maddali, Sunil Laxman
Liquid chromatography-mass spectrometry (LC-MS/MS) based approaches are widely used for the identification and quantitation of specific metabolites, and are a preferred approach towards analyzing cellular metabolism. Most methods developed come with specific requirements such as unique columns, ion-pairing reagents and pH conditions, and typically allow measurements in a specific pathway alone. Here, we present a single column-based set of methods for simultaneous coverage of multiple pathways, primarily focusing on central carbon, amino acid, and nucleotide metabolism...
2018: Wellcome Open Research
Tatiana Dudnakova, Hywel Dunn-Davies, Rosie Peters, David Tollervey
Background: Recent analyses implicate changes in the expression of the box C/D class of small nucleolar RNAs (snoRNAs) in several human diseases. Methods: Here we report the identification of potential novel RNA targets for box C/D snoRNAs in budding yeast, using the approach of UV crosslinking and sequencing of hybrids (CLASH) with the snoRNP proteins Nop1, Nop56 and Nop58. We also developed a bioinformatics approach to filter snoRNA-target interactions for bona fide methylation guide interactions. Results: We recovered 241,420 hybrids, out of which 190,597 were classed as reproducible, high energy hybrids...
2018: Wellcome Open Research
Andy Boyd, Matthew Woollard, John Macleod, Alison Park
Historical records and the research databases of completed studies have the potential either to establish new research studies or to inform follow-up studies assessing long-term health and social outcomes. Yet, such records are at risk of destruction resulting from misconceptions about data protection legislation and research ethics. The recent destruction of the Windrush disembarkation cards, which potentially could have formed the basis of a retrospective cohort study, illustrates this risk. As organisations across Europe transition to the EU General Data Protection Regulation (GDPR), this risk is being amplified due to uncertainty as to how to comply with complex new rules, and the requirement under GDPR that data owners catalogue their data and set data retention and destruction rules...
2018: Wellcome Open Research
Zoe V J Woodhead, Holly A Rutherford, Dorothy V M Bishop
Background: Relative blood flow in the two middle cerebral arteries can be measured using functional transcranial Doppler sonography (fTCD) to give an index of lateralisation as participants perform a specific task. Language laterality has mostly been studied with fTCD using a word generation task, but it is not clear whether this is optimal. Methods: Using fTCD, we evaluated a sentence generation task that has shown good reliability and strong left lateralisation in fMRI. We interleaved trials of word generation, sentence generation and list generation and assessed agreement of these tasks in 31 participants (29 right-handers)...
2018: Wellcome Open Research
Haleema Shakur-Still, Ian Roberts, Bukola Fawole, Modupe Kuti, Oladapo O Olayemi, Adenike Bello, Sumaya Huque, Olayinka Ogunbode, Taiwo Kotila, Chris Aimakhu, Olujide A Okunade, Tolulase Olutogun, Cecilia O Adetayo, Kastriot Dallaku, Ulrich Mansmann, Beverley J Hunt, Tracey Pepple, Eni Balogun
Background: Postpartum haemorrhage (PPH) is a leading cause of maternal death. The WOMAN trial showed that tranexamic acid (TXA) reduces death due to bleeding in women with PPH. We evaluated the effect of TXA on fibrinolysis and coagulation in a sample of WOMAN trial participants. Methods: Adult women with a clinical diagnosis of PPH were randomised to receive 1 g TXA or matching placebo in the WOMAN trial. Participants in the WOMAN trial at University College Hospital (Ibadan, Nigeria) also had venous blood taken just before administration of the first dose of trial treatment and again 30 (±15) min after the first dose (the ETAC study)...
2018: Wellcome Open Research
M Kirthiga, M S Muthu, G Kayalvizhi, C Krithika
Background: Contact areas in primary teeth are known to be broader, flatter, and situated more gingivally than in permanent teeth. The objective of the present study was to evaluate the different types of intact contact areas in primary teeth using cone beam computed tomography (CBCT) among children. Methods: A cross-sectional study was designed with 74 contacts from 28 existing CBCT images of patients aged between 3 and 14 years, obtained from the Indian Dental Education Academy, Chennai, India. The shape of the contact area was observed at three levels, the coronal, middle, and apical thirds, in three different sections of CBCT...
2018: Wellcome Open Research
Laura J Shallcross, Alexander Mentzer, Saadia Rahman, Graham S Cooke, Shiranee Sriskandan, Mahdad Noursadeghi
Introduction: Infectious diseases have a major impact on morbidity and mortality in hospital. Microbial diagnosis remains elusive for most cases of suspected infection which impacts on the use of antibiotics. Rapid advances in genomic technologies combined with high-quality phenotypic data have great potential to improve the diagnosis, management and clinical outcomes of infectious diseases.  The aim of the Bioresource in Adult Infectious Diseases (BioAID) is to provide a platform for biomarker discovery, trials and clinical service developments in the field of infectious diseases, by establishing a registry linking clinical phenotype to microbial and biological samples in adult patients who attend hospital with suspected infection...
2018: Wellcome Open Research
Kevin Walsh, Nuala Calder, Peter Olupot-Olupot, Tonny Ssenyondo, William Okiror, Charles Bernard Okalebo, Rita Muhindo, Ayub Mpoya, Elaine Holmes, Julian Marchesi, Gael Delamare de la Villenaise de Chenevarin, Gary Frost, Kathryn Maitland
Background: Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome...
2018: Wellcome Open Research
Gerry Tonkin-Hill, John A Lees, Stephen D Bentley, Simon D W Frost, Jukka Corander
Identifying structure in collections of sequence data sets remains a common problem in genomics. hierBAPS, a popular algorithm for identifying population structure in haploid genomes, has previously only been available as a MATLAB binary. We provide an R implementation which is both easier to install and use, automating the entire pipeline. Additionally, we allow for the use of multiple processors, improve on the default settings of the algorithm, and provide an interface with the ggtree library to enable informative illustration of the clustering results...
2018: Wellcome Open Research
Suceena Alexander, George T John, Anila Korula, T S Vijayakumar, Vinoi George David, Anjali Mohapatra, Anna T Valson, Shibu Jacob, Pradeep Mathew Koshy, Gautam Rajan, Elenjickal Elias John, Smita Mary Matthai, L Jeyaseelan, Babu Ponnusamy, Terence Cook, Charles Pusey, Mohamed R Daha, John Feehally, Jonathan Barratt, Santosh Varughese
Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world...
2018: Wellcome Open Research
Monika Frysz, Laura D Howe, Jonathan H Tobias, Lavinia Paternoster
Puberty is a time of substantial biological and psychological changes. One of the hallmarks of puberty is a rapid growth spurt, however its timing varies between individuals. The impact of pubertal timing on later health outcomes has been of interest in life course epidemiology, however its measurement can be challenging. Age at peak height velocity (aPHV) offers an objective measure of pubertal timing without having to rely on physical examination or self-report. We describe the derivation of aPHV estimates in Avon Longitudinal Study of Parents and Children (ALSPAC) offspring, using Superimposition by Translation And Rotation (SITAR) mixed effects growth curve analysis...
2018: Wellcome Open Research
Rachel R Atherton, Jayne Ellis, Fiona V Cresswell, Joshua Rhein, David R Boulware
Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials...
2018: Wellcome Open Research
Meghan B Azad, Kaitlin H Wade, Nicholas J Timpson
Background: The FUT2 (fucosyltransferase 2) gene encodes alpha (1,2) fucosyltransferase, which determines blood group secretor status. Being homozygous for the inactive "non-secretor" rs601338(A) allele appears to confer resistance to certain infections (e.g. Norovirus , Rotavirus and Helicobacter pylori ) and susceptibility to others (e.g. Haemophilus influenza and Streptococcus pneumonia ). Non-secretors also have an increased risk of type 1 diabetes and inflammatory bowel disease. We aimed to determine the association of the FUT2 secretor genotype with infections and chronic conditions in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC)...
2018: Wellcome Open Research
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