bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human leukocyte antigen B*0702 is protective against ocular Stevens–Johnson syndrome/toxic epidermal necrolysis in the UK population
Authors: Butt Gibran F. , Hassan Ali , Wallace Graham R. , Kinoshita Shigeru , Ahmad Sajjad , Ueta Mayumi , Rauz Saaeha 
Published: February 2021

AbstractStevens–Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are part of a disease continuum of vesiculobullous mucocutaneous reactions affecting the skin and mucous membranes including the ocular surface. Manifestations of disease range from mild dry eye to progressive conjunctival cicatrisation, limbal epithelial stem cell failure and corneal blindness. In Far Eastern and South East Asian populations where SJS/TEN is prevalent, numerous human leukocyte antigen (HLA) gene variants at the A, B and C loci have been identified as risk factors for developing SJS/TEN with severe ocular complications (SOC). By contrast, the incidence of SJS/TEN with SOC in European countries is relatively low. To date, ocular SJS/TEN risk altering alleles have not been widely investigated in European populations. In this study, we analysed the association of HLA -A, -B and -C alleles with SJS/TEN in 33 patients residing in the UK with age matched controls. The data showed statistically significant novel negative allele association with HLA-B*0702 and a trend with HLA-C*0702 in the patient group, indicating these alleles are protective. Further characterisation of protective and risk alleles in other ethnic groups is required to fully elucidate the putative role of these alleles in the susceptibility of SJS/TEN with or without severe ocular complications in patients in the UK.
Characterization of a green Stentor with symbiotic algae growing in an extremely oligotrophic environment and storing large amounts of starch granules in its cytoplasm
Authors: Hoshina Ryo , Tsukii Yuuji , Harumoto Terue , Suzaki Toshinobu 
Published: February 2021

AbstractThe genus Stentor is a relatively well-known ciliate owing to its lucid trumpet shape. Stentor pyriformis represents a green, short, and fat Stentor, but it is a little-known species. We investigated 124 ponds and wetlands in Japan and confirmed the presence of S. pyriformis at 23 locations. All these ponds were noticeably oligotrophic. With the improvement of oligotrophic culture conditions, we succeeded in long-term cultivation of three strains of S. pyriformis. The cytoplasm of S. piriformis contains a large number of 1–3 μm refractive granules that turn brown by Lugol’s staining. The granules also show a typical Maltese-cross pattern by polarization microscopy, strongly suggesting that the granules are made of amylopectin-rich starch. By analyzing the algal rDNA, it was found that all S. pyriformis symbionts investigated in this study were Chlorella variabilis. This species is known as the symbiont of Paramecium bursaria and is physiologically specialized for endosymbiosis. Genetic discrepancies between C. variabilis of S. pyriformis and P. bursaria may indicate that algal sharing was an old incident. Having symbiotic algae and storing carbohydrate granules in the cytoplasm is considered a powerful strategy for this ciliate to withstand oligotrophic and cold winter environments in highland bogs.
A molecularly defined skin test reagent for the diagnosis of bovine tuberculosis compatible with vaccination against Johne’s Disease
Authors: Middleton Sonya , Steinbach Sabine , Coad Michael , McGill Kevina , Brady Colm , Duignan Anthony , Wiseman Jimmy , Gormley Eamonn , Jones Gareth J. , Vordermeier H. Martin 
Published: February 2021

AbstractTuberculin Purified Protein Derivatives (PPDs) exhibit multiple limitations: they are crude extracts from mycobacterial cultures with largely unknown active components; their production depends on culture of mycobacteria requiring expensive BCL3 production facilities; and their potency depends on the technically demanding guinea pig assay. To overcome these limitations, we developed a molecularly defined tuberculin (MDT) by adding further antigens to our prototype reagent composed of ESAT-6, CFP-10 and Rv3615c (DIVA skin test, DST). In vitro screening using PBMC from infected and uninfected cattle shortlisted four antigens from a literature-based list of 18 to formulate the MDT. These four antigens plus the previously identified Rv3020c protein, produced as recombinant proteins or overlapping synthetic peptides, were formulated together with the three DST antigens into the MDT to test cattle experimentally and naturally infected with M. bovis, uninfected cattle and MAP vaccinated calves. We demonstrated significant increases in MDT-induced skin responses compared to DST in infected animals, whilst maintaining high specificity in unvaccinated or MAP vaccinated calves. Further, MDT can also be applied in in vitro blood-based interferon-gamma release assays. Thus, MDT promises to be a robust diagnostic skin and blood test reagent overcoming some of the limitations of PPDs and warrants full validation.
Urine lipoarabinomannan in HIV uninfected, smear negative, symptomatic TB patients: effective sample pretreatment for a sensitive immunoassay and mass spectrometry
Authors: Amin Anita G. , De Prithwiraj , Graham Barbara , Calderon Roger I. , Franke Molly F. , Chatterjee Delphi 
Published: February 2021

AbstractOur study sought to determine whether urine lipoarabinomannan (LAM) could be validated in a sample cohort that consisted mainly of HIV uninfected individuals that presented with tuberculosis symptoms. We evaluated two tests developed in our laboratory, and used them on clinical samples from Lima, Peru where incidence of HIV is low. ELISA analysis was performed on 160 samples (from 140 adult culture-confirmed TB cases and 20 symptomatic TB-negative child controls) using 100 μL of urine after pretreatment with Proteinase K. Two different mouse monoclonal antibodies-CS35 and CHCS9-08 were used individually for capture of urine LAM. Among cases, optical density (OD450) values had a positive association with higher bacillary loads. The 20 controls had negative values (below the limit of detection). The assay correctly identified all samples (97–100% accuracy confidence interval). For an alternate validation of the ELISA results, we analyzed all 160 urine samples using an antibody independent chemoanalytical approach. Samples were called positive only when LAM surrogates—tuberculostearic acid (TBSA) and d-arabinose (d-ara)—were found to be present in similar amounts. All TB cases, including the 40 with a negative sputum smear had LAM in detectable quantities in urine. None of the controls had detectable amounts of LAM. Our study shows that urinary LAM detection is feasible in HIV uninfected, smear negative TB patients.
Unravelling the involvement of cilevirus p32 protein in the viral transport
Authors: Leastro Mikhail Oliveira , Freitas-Astúa Juliana , Kitajima Elliot Watanabe , Pallás Vicente , Sánchez-Navarro Jesús A. 
Published: February 2021

AbstractCitrus leprosis (CL) is a severe disease that affects citrus orchards mainly in Latin America. It is caused by Brevipalpus-transmitted viruses from genera Cilevirus and Dichorhavirus. Currently, no reports have explored the movement machinery for the cilevirus. Here, we have performed a detailed functional study of the p32 movement protein (MP) of two cileviruses. Citrus leprosis-associated viruses are not able to move systemically in neither their natural nor experimental host plants. However, here we show that cilevirus MPs are able to allow the cell-to-cell and long-distance transport of movement-defective alfalfa mosaic virus (AMV). Several features related with the viral transport were explored, including: (i) the ability of cilevirus MPs to facilitate virus movement on a nucleocapsid assembly independent-manner; (ii) the generation of tubular structures from transient expression in protoplast; (iii) the capability of the N- and C- terminus of MP to interact with the cognate capsid protein (p29) and; (iv) the role of the C-terminus of p32 in the cell-to-cell and long-distance transport, tubule formation and the MP-plasmodesmata co-localization. The MP was able to direct the p29 to the plasmodesmata, whereby the C-terminus of MP is independently responsible to recruit the p29 to the cell periphery. Furthermore, we report that MP possess the capacity to enter the nucleolus and to bind to a major nucleolar protein, the fibrillarin. Based on our findings, we provide a model for the role of the p32 in the intra- and intercellular viral spread.
Data-driven identification of ageing-related diseases from electronic health records
Authors: Kuan Valerie , Fraser Helen C. , Hingorani Melanie , Denaxas Spiros , Gonzalez-Izquierdo Arturo , Direk Kenan , Nitsch Dorothea , Mathur Rohini , Parisinos Constantinos A. , Lumbers R. Thomas , Sofat Reecha , Wong Ian C. K. , Casas Juan P. , Thornton Janet M. , Hemingway Harry , Partridge Linda , Hingorani Aroon D. 
Published: February 2021

AbstractReducing the burden of late-life morbidity requires an understanding of the mechanisms of ageing-related diseases (ARDs), defined as diseases that accumulate with increasing age. This has been hampered by the lack of formal criteria to identify ARDs. Here, we present a framework to identify ARDs using two complementary methods consisting of unsupervised machine learning and actuarial techniques, which we applied to electronic health records (EHRs) from 3,009,048 individuals in England using primary care data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics admitted patient care dataset between 1 April 2010 and 31 March 2015 (mean age 49.7 years (s.d. 18.6), 51% female, 70% white ethnicity). We grouped 278 high-burden diseases into nine main clusters according to their patterns of disease onset, using a hierarchical agglomerative clustering algorithm. Four of these clusters, encompassing 207 diseases spanning diverse organ systems and clinical specialties, had rates of disease onset that clearly increased with chronological age. However, the ages of onset for these four clusters were strikingly different, with median age of onset 82 years (IQR 82–83) for Cluster 1, 77 years (IQR 75–77) for Cluster 2, 69 years (IQR 66–71) for Cluster 3 and 57 years (IQR 54–59) for Cluster 4. Fitting to ageing-related actuarial models confirmed that the vast majority of these 207 diseases had a high probability of being ageing-related. Cardiovascular diseases and cancers were highly represented, while benign neoplastic, skin and psychiatric conditions were largely absent from the four ageing-related clusters. Our framework identifies and clusters ARDs and can form the basis for fundamental and translational research into ageing pathways.
Mercury in the human adrenal medulla could contribute to increased plasma noradrenaline in aging
Authors: Pamphlett Roger , Kum Jew Stephen , Doble Philip A. , Bishop David P. 
Published: February 2021

AbstractPlasma noradrenaline levels increase with aging, and this could contribute to the sympathetic overactivity that is associated with essential hypertension and the metabolic syndrome. The underlying cause of this rise in noradrenaline is unknown, but a clue may be that mercury increases noradrenaline output from the adrenal medulla of experimental animals. We therefore determined the proportion of people from 2 to 104 years of age who had mercury in their adrenal medulla. Mercury was detected in paraffin sections of autopsied adrenal glands using two methods of elemental bioimaging, autometallography and laser ablation-inductively coupled plasma-mass spectrometry. Mercury first appeared in cells of the adrenal medulla in the 21–40 years group, where it was present in 52% of samples, and increased progressively in frequency in older age groups, until it was detected in 90% of samples from people aged over 80 years. In conclusion, the proportion of people having mercury in their adrenal medulla increases with aging. Mercury could alter the metabolism of catecholamines in the adrenal medulla that leads to the raised levels of plasma noradrenaline in aging. This retrospective autopsy study was not able to provide a definitive link between adrenal mercury, noradrenaline levels and hypertension, but future functional human and experimental studies could provide further evidence for these associations.
Immature symbiotic system between horizontally transmitted green algae and brown hydra
Authors: Miyokawa Ryo , Kanaya Hiroyuki J. , Itoh Taichi Q. , Kobayakawa Yoshitaka , Kusumi Junko 
Published: February 2021

AbstractSome strains of brown hydra (Hydra vulgaris) are able to harbor the green algae Chlorococcum in their endodermal epithelial cells as symbionts. However, the relationship between brown hydra and chlorococcum is considered to be incipient symbiosis because most artificially introduced symbionts are not stable and because symbiotic H. vulgaris strains are rare in the wild. In this study, we compared the gene expression levels of the newly established symbiotic hydra (strain 105G), the native symbiotic strain (J7), and their non-symbiotic polyps to determine what changes would occur at the early stage of the evolution of symbiosis. We found that both the 105G and J7 strains showed comparable expression patterns, exhibiting upregulation of lysosomal enzymes and downregulation of genes related to nematocyte development and function. Meanwhile, genes involved in translation and the respiratory chain were upregulated only in strain 105G. Furthermore, treatment with rapamycin, which inhibits translation activity, induced the degeneration of the symbiotic strains (105G and J7). This effect was severe in strain 105G. Our results suggested that evolving the ability to balance the cellular metabolism between the host and the symbiont is a key requirement for adapting to endosymbiosis with chlorococcum.
Risk factors analysis of COVID-19 patients with ARDS and prediction based on machine learning
Authors: Xu Wan , Sun Nan-Nan , Gao Hai-Nv , Chen Zhi-Yuan , Yang Ya , Ju Bin , Tang Ling-Ling 
Published: February 2021

AbstractCOVID-19 is a newly emerging infectious disease, which is generally susceptible to human beings and has caused huge losses to people's health. Acute respiratory distress syndrome (ARDS) is one of the common clinical manifestations of severe COVID-19 and it is also responsible for the current shortage of ventilators worldwide. This study aims to analyze the clinical characteristics of COVID-19 ARDS patients and establish a diagnostic system based on artificial intelligence (AI) method to predict the probability of ARDS in COVID-19 patients. We collected clinical data of 659 COVID-19 patients from 11 regions in China. The clinical characteristics of the ARDS group and no-ARDS group of COVID-19 patients were elaborately compared and both traditional machine learning algorithms and deep learning-based method were used to build the prediction models. Results indicated that the median age of ARDS patients was 56.5 years old, which was significantly older than those with non-ARDS by 7.5 years. Male and patients with BMI > 25 were more likely to develop ARDS. The clinical features of ARDS patients included cough (80.3%), polypnea (59.2%), lung consolidation (53.9%), secondary bacterial infection (30.3%), and comorbidities such as hypertension (48.7%). Abnormal biochemical indicators such as lymphocyte count, CK, NLR, AST, LDH, and CRP were all strongly related to the aggravation of ARDS. Furthermore, through various AI methods for modeling and prediction effect evaluation based on the above risk factors, decision tree achieved the best AUC, accuracy, sensitivity and specificity in identifying the mild patients who were easy to develop ARDS, which undoubtedly helped to deliver proper care and optimize use of limited resources.
Biochemical and cellular characterisation of the Plasmodium falciparum M1 alanyl aminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP)
Authors: Mathew Rency , Wunderlich Juliane , Thivierge Karine , Cwiklinski Krystyna , Dumont Claire , Tilley Leann , Rohrbach Petra , Dalton John P. 
Published: February 2021

AbstractThe Plasmodium falciparum M1 alanyl aminopeptidase and M17 leucyl aminopeptidase, PfM1AAP and PfM17LAP, are potential targets for novel anti-malarial drug development. Inhibitors of these aminopeptidases have been shown to kill malaria parasites in culture and reduce parasite growth in murine models. The two enzymes may function in the terminal stages of haemoglobin digestion, providing free amino acids for protein synthesis by the rapidly growing intra-erythrocytic parasites. Here we have performed a comparative cellular and biochemical characterisation of the two enzymes. Cell fractionation and immunolocalisation studies reveal that both enzymes are associated with the soluble cytosolic fraction of the parasite, with no evidence that they are present within other compartments, such as the digestive vacuole (DV). Enzyme kinetic studies show that the optimal pH of both enzymes is in the neutral range (pH 7.0–8.0), although PfM1AAP also possesses some activity (< 20%) at the lower pH range of 5.0–5.5. The data supports the proposal that PfM1AAP and PfM17LAP function in the cytoplasm of the parasite, likely in the degradation of haemoglobin-derived peptides generated in the DV and transported to the cytosol.
Operant conditioning deficits and modified local field potential activities in parvalbumin-deficient mice
Authors: Lintas Alessandra , Sánchez-Campusano Raudel , Villa Alessandro E. P. , Gruart Agnès , Delgado-García José M. 
Published: February 2021

AbstractAltered functioning of GABAergic interneurons expressing parvalbumin (PV) in the basal ganglia-thalamo-cortical circuit are likely to be involved in several human psychiatric disorders characterized by deficits in attention and sensory gating with dysfunctional decision-making behavior. However, the contribution of these interneurons in the ability to acquire demanding learning tasks remains unclear. Here, we combine an operant conditioning task with local field potentials simultaneously recorded in several nuclei involved in reward circuits of wild-type (WT) and PV-deficient (PVKO) mice, which are characterized by changes in firing activity of PV-expressing interneurons. In comparison with WT mice, PVKO animals presented significant deficits in the acquisition of the selected learning task. Recordings from prefrontal cortex, nucleus accumbens (NAc) and hippocampus showed significant decreases of the spectral power in beta and gamma bands in PVKO compared with WT mice particularly during the performance of the operant conditioning task. From the first to the last session, at all frequency bands the spectral power in NAc tended to increase in WT and to decrease in PVKO. Results indicate that PV deficiency impairs signaling necessary for instrumental learning and the recognition of natural rewards.
Genome-wide analysis of allele-specific expression of genes in the model diatom Phaeodactylum tricornutum
Authors: Hoguin Antoine , Rastogi Achal , Bowler Chris , Tirichine Leila 
Published: February 2021

AbstractRecent advances in next generation sequencing technologies have allowed the discovery of widespread autosomal allele-specific expression (aASE) in mammals and plants with potential phenotypic effects. Extensive numbers of genes with allele-specific expression have been described in the diatom Fragilariopsis cylindrus in association with adaptation to external cues, as well as in Fistulifera solaris in the context of natural hybridization. However, the role of aASE and its extent in diatoms remain elusive. In this study, we investigate allele-specific expression in the model diatom Phaeodactylum tricornutum by the re-analysis of previously published whole genome RNA sequencing data and polymorphism calling. We found that 22% of P. tricornutum genes show moderate bias in allelic expression while 1% show nearly complete monoallelic expression. Biallelic expression associates with genes encoding components of protein metabolism while moderately biased genes associate with functions in catabolism and protein transport. We validated candidate genes by pyrosequencing and found that moderate biases in allelic expression were less stable than monoallelically expressed genes that showed consistent bias upon experimental validations at the population level and in subcloning experiments. Our approach provides the basis for the analysis of aASE in P. tricornutum and could be routinely implemented to test for variations in allele expression under different environmental conditions.
High-temporal-resolution quasideterministic dynamics of granular stick-slip
Authors: Nguyen T. T. T. , Doanh T. , Le Bot A. , Dalmas D. 
Published: February 2021

AbstractWe report high-temporal-resolution observations of the spontaneous instability of model granular materials under isotropic and triaxial compression in fully drained conditions during laboratory tests representative of earthquakes. Unlike in natural granular materials, in the model granular materials, during the first stage of the tests, i.e., isotropic compression, a series of local collapses of various amplitudes occurs under random triggering cell pressures. During the second stage, i.e., shearing under triaxial compression, the model granular samples exhibit very large quasiperiodic stick-slip motions at random deviatoric triggering stresses. These motions are responsible for very large stress drops that are described by power laws and are accurate over more than 3 decades in logarithmic space. Then, we identify the quasideterministic nature of these stick-slip events, assuming that they are fully controlled by the cell pressure and solid fraction. Finally, we discuss the potential mechanisms that could explain these intriguing behaviors and the possible links with natural earthquakes.
Production of bacterial cellulose using Gluconacetobacter kombuchae immobilized on Luffa aegyptiaca support
Authors: Rahman Sameeha Syed Abdul , Vaishnavi T. , Vidyasri G. Sai , Sathya K. , Priyanka P. , Venkatachalam Ponnusami , Karuppiah Sugumaran 
Published: February 2021

AbstractThe present work report for the first time on the production of bacterial cellulose (BC) using natural loofa sponge (Luffa aegyptiaca) as a scaffold for the immobilization ofGluconacetobacter kombuchae. Bacterial cellulose (BC) are recently gained more attention in several fields including biological and biomedical applications due to their outstanding physico-chemical characteristics including high thermal stability, easy biodegradability, good water holding capacity, high tensile strength, and high degree of polymerization. The increase in requirement of alternative method for the enhancement of BC production under economical aspect develops a positive impact in large scale industries. In this study,Luffa aegyptiaca(LA) was introduced in a separate fermentation medium so as to enhance the concentration of BC production byGluconacetobacter kombuchae. Different process/medium parameters such as initial pH, static/shaking condition, inoculum size, nitrogen source, C/N ratio, supplements (ethanol and acetic acid) were analysed for the production of bacterial cellulose using LA support. The maximum yield of BC was obtained using following condition: culturing condition -shaking; initial pH − 5.5; nitrogen source- yeast extract, C/N ratio – 40 and supplement—ethanol. The characterization of the BC was examined using Fourier Transform Infra-Red spectroscopy and thermo gravimetric analysis. The biofilm formation on the surface of LA was examined by SEM photographs. Thus, implementation of LA as a support in shaking fermentation under suitable medium/process variables enhanced the BC production.