bluuebunny/crossref_metadata_2025_split huggingface dataset:
TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection
Authors: Amrun Siti Naqiah , Tan Jeslin J. L. , Rickett Natasha Y. , Cox Jonathan A. , Lee Bernett , Griffiths Michael J. , Solomon Tom , Perera David , Ooi Mong How , Hiscox Julian A. , Ng Lisa F. P. 
Published: March 2020

AbstractHand, foot and mouth disease (HFMD), caused by enterovirus A71 (EV-A71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV-A71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterised in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV-A71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV-A71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signalling. Depletion of TREM-1 in EV-A71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV-A71 infections in primary human cells, and the potential involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.
Complex approach for analysis of snake venom α-neurotoxins binding to HAP, the high-affinity peptide
Authors: Kudryavtsev Denis S. , Tabakmakher Valentin М. , Budylin Gleb S. , Egorova Natalia S. , Efremov Roman G. , Ivanov Igor A. , Belukhina Svetlana Yu. , Jegorov Artjom V. , Kasheverov Igor E. , Kryukova Elena V. , Shelukhina Irina V. , Shirshin Evgeny A. , Zhdanova Nadezhda G. , Zhmak Maxim N. , Tsetlin Victor I. 
Published: March 2020

AbstractSnake venom α-neurotoxins, invaluable pharmacological tools, bind with high affinity to distinct subtypes of nicotinic acetylcholine receptor. The combinatorial high-affinity peptide (HAP), homologous to the C-loop of α1 and α7 nAChR subunits, binds biotinylated α-bungarotoxin (αBgt) with nanomolar affinity and might be a protection against snake-bites. Since there are no data on HAP interaction with other toxins, we checked its binding of α-cobratoxin (αCtx), similar to αBgt in action on nAChRs. Using radioiodinated αBgt, we confirmed a high affinity of HAP for αBgt, the complex formation is supported by mass spectrometry and gel chromatography, but only weak binding was registered with αCtx. A combination of protein intrinsic fluorescence measurements with the principal component analysis of the spectra allowed us to measure the HAP-αBgt binding constant directly (29 nM). These methods also confirmed weak HAP interaction with αCtx (>10000 nM). We attempted to enhance it by modification of HAP structure relying on the known structures of α-neurotoxins with various targets and applying molecular dynamics. A series of HAP analogues have been synthesized, HAP[L9E] analogue being considerably more potent than HAP in αCtx binding (7000 nM). The proposed combination of experimental and computational approaches appears promising for analysis of various peptide-protein interactions.
A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals
Authors: Liu Peng , Smith Benjamin R. , Montonye Michelle L. , Kemper Lisa J. , Leinonen-Wright Kailee , Nelson Kathryn M. , Higgins LeeAnn , Guerrero Candace R. , Markowski Todd W. , Zhao Xiaohui , Petersen Ashley J. , Knopman David S. , Petersen Ronald C. , Ashe Karen H. 
Published: March 2020

AbstractNeurofibrillary tangles are a pathological hallmark of Alzheimer’s disease, and their levels correlate with the severity of cognitive dysfunction in humans. However, experimental evidence suggests that soluble tau species cause cognitive deficits and memory impairment. Our recent study suggests that caspase-2 (Casp2)-catalyzed tau cleavage at aspartate 314 mediates synaptic dysfunction and memory impairment in mouse and cellular models of neurodegenerative disorders. Δtau314, the C-terminally-truncated cleavage products, are soluble and present in human brain. In addition, levels of Δtau314 proteins are elevated in the brain of the cognitively impaired individuals compared to the cognitively normal individuals, indicating a possible role for Δtau314 proteins in cognitive deterioration. Here we show that (1) Δtau314 proteins are present in the inferior temporal gyrus of human brains; (2) Δtau314 proteins are generated from all six tau splicing isoforms, (3) levels of both Casp2 and Δtau314 proteins are elevated in cognitively impaired individuals compared to cognitively normal individuals, and (4) levels of Δtau314 proteins show a modest predictive value for dementia. These findings advance our understanding of the characteristics of Δtau314 proteins and their relevance to cognitive dysfunction and shed light on the contribution of Casp2-mediated Δtau314 production to cognitive deterioration.
Basic Hallmarks of Urothelial Cancer Unleashed in Primary Uroepithelium by Interference with the Epigenetic Master Regulator ODC1
Authors: Erichsen Lars , Seifert Hans-Helge , Schulz Wolfgang A. , Hoffmann Michèle J. , Niegisch Günter , Araúzo-Bravo Marcos J. , Bendhack Marcelo L. , Poyet Cedric , Hermanns Thomas , Beermann Agnes , Hassan Mohamed , Theis Lisa , Mahmood Wardah , Santourlidis Simeon 
Published: March 2020

AbstractUrothelial carcinoma (UC) is a common disease causing significant morbidity and mortality as well as considerable costs for health systems. Extensive aberrant methylation of DNA is broadly documented in early UC, contributing to genetic instability, altered gene expression and tumor progression. However the triggers initiating aberrant methylation are unknown. Recently we discovered that several genes encoding key enzymes of methyl group and polyamine metabolism, including Ornithine Decarboxylase 1(ODC1), are affected by DNA methylation in early stage UC. In this study, we investigated the hypothesis that these epigenetic alterations act in a feed-forward fashion to promote aberrant DNA methylation in UC. We demonstrate that siRNA-mediated knockdown ofODC1expression elicits genome-wide LINE-1 demethylation, induction of LINE-1 transcripts and double-strand DNA breaks and decreases viability in primary cultured uroepithelial cells. Similarly, following siRNA-mediated knockdown ofODC1, UC cells undergo double-strand DNA breaks and apoptosis. Collectively, our findings provide evidence thatODC1gene hypermethylation could be a starting point for the onset of genome-wide epigenetic aberrations in urothelial carcinogenesis. Furthermore, LINE-1 induction enabled byODC1interference provides a new experimental model to study mechanisms and consequences of LINE-1 activation in the etiology and progression of UC as well as presumably other cancers.
The LRRK2 N-terminal domain influences vesicle trafficking: impact of the E193K variant
Authors: Marku Algerta , Carrion Maria Dolores Perez , Pischedda Francesca , Marte Antonella , Casiraghi Zeila , Marciani Paola , von Zweydorf Felix , Gloeckner Christian Johannes , Onofri Franco , Perego Carla , Piccoli Giovanni 
Published: March 2020

AbstractThe LRRK2 protein consists of multiple functional domains, including protein-binding domains at its N and C-terminus. Mutations in the Leucine-rich repeat kinase 2 gene (LRRK2) have been linked to familial and sporadic Parkinson’s disease (PD). We have recently described a novel variant falling within the N-terminal armadillo repeats, E193K. Herein, our aim is to investigate the functional impact of LRRK2 N-terminal domain and the E193K variant on vesicle trafficking. By combining Total Internal Reflection Fluorescence (TIRF) microscopy and a synaptopHluorin assay, we found that expression of a construct lacking the N-terminal domain increases the frequency and amplitude of spontaneous synaptic events. Complementary biochemical approaches showed that the E193K variant alters the binding properties of LRRK2, decreases LRRK2 binding to synaptic vesicles, and promotes vesicle fusion. Our results confirm the physiological and pathological relevance of the nature of the LRRK2-associated macro-molecular complex solidifying the idea that different pathological mutations critically alter the scaffolding function of LRRK2 resulting in a perturbation of the vesicular trafficking as a common denominator.
Generation of Non-aliased Two-dimensional Acoustic Vortex with Enclosed Metasurface
Authors: Liu Jing-jing , Liang Bin , Yang Jing , Yang Jun , Cheng Jian-chun 
Published: March 2020

AbstractTwo-dimensional (2D) acoustic vortex allows new physics and applications different from three-dimensional counterparts, yet existing mechanisms usually have to rely on active array composed of transducers which may result in complexity, high cost and, in particular, undesired spatial aliasing effect. We propose to generate 2D acoustic vortex inside an enclosed metasurface illuminated by axisymmetric wave carrying no orbital angular momentum. We derive the criterion on unit size for eliminating spatial aliasing effect which is challenging for conventional active approaches and design a membrane-based metasurface to implement our mechanism. The performance of our strategy is demonstrated via precise production of different orders of non-aliased vortices regardless of center-to-center alignment, with undistorted Bessel-like pattern extending to the whole inner region. We anticipate our design with simplicity, compactness, precision and flexibility to open up possibility to design novel vortex devices and find important applications in diverse scenarios such as on-chip particle manipulations.
Neotropical termite microbiomes as sources of novel plant cell wall degrading enzymes
Authors: Romero Victorica Matias , Soria Marcelo A. , Batista-García Ramón Alberto , Ceja-Navarro Javier A. , Vikram Surendra , Ortiz Maximiliano , Ontañon Ornella , Ghio Silvina , Martínez-Ávila Liliana , Quintero García Omar Jasiel , Etcheverry Clara , Campos Eleonora , Cowan Donald , Arneodo Joel , Talia Paola M. 
Published: March 2020

AbstractIn this study, we used shotgun metagenomic sequencing to characterise the microbial metabolic potential for lignocellulose transformation in the gut of two colonies of Argentine higher termite species with different feeding habits, Cortaritermes fulviceps and Nasutitermes aquilinus. Our goal was to assess the microbial community compositions and metabolic capacity, and to identify genes involved in lignocellulose degradation. Individuals from both termite species contained the same five dominant bacterial phyla (Spirochaetes, Firmicutes, Proteobacteria, Fibrobacteres and Bacteroidetes) although with different relative abundances. However, detected functional capacity varied, with C. fulviceps (a grass-wood-feeder) gut microbiome samples containing more genes related to amino acid metabolism, whereas N. aquilinus (a wood-feeder) gut microbiome samples were enriched in genes involved in carbohydrate metabolism and cellulose degradation. The C. fulviceps gut microbiome was enriched specifically in genes coding for debranching- and oligosaccharide-degrading enzymes. These findings suggest an association between the primary food source and the predicted categories of the enzymes present in the gut microbiomes of each species. To further investigate the termite microbiomes as sources of biotechnologically relevant glycosyl hydrolases, a putative GH10 endo-β-1,4-xylanase, Xyl10E, was cloned and expressed in Escherichia coli. Functional analysis of the recombinant metagenome-derived enzyme showed high specificity towards beechwood xylan (288.1 IU/mg), with the optimum activity at 50 °C and a pH-activity range from 5 to 10. These characteristics suggest that Xy110E may be a promising candidate for further development in lignocellulose deconstruction applications.
Reliability of CT radiomic features reflecting tumour heterogeneity according to image quality and image processing parameters
Authors: Park Bum Woo , Kim Jeong Kon , Heo Changhoe , Park Kye Jin 
Published: March 2020

AbstractThe reliability of radiomics features (RFs) is crucial for quantifying tumour heterogeneity. We assessed the influence of imaging, segmentation, and processing conditions (quantization range, bin number, signal-to-noise ratio [SNR], and unintended outliers) on RF measurement. Low SNR and unintended outliers increased the standard deviation and mean values of histograms to calculate the first-order RFs. Variations in imaging processing conditions significantly altered the shape of the probability distribution (centre of distribution, extent of dispersion, and segmentation of probability clusters) in second-order RF matrices (i.e. grey-level co-occurrence and grey-level run length), thereby eventually causing fluctuations in RF estimation. Inconsistent imaging and processing conditions decreased the number of reliably measured RFs in terms of individual RF values (intraclass correlation coefficient ≥0.75) and inter-lesion RF ratios (coefficient of variation <15%). No RF could be reliably estimated under inconsistent SNR and inclusion of outlier conditions. By contrast, with high SNR and no outliers, all first-order RFs, 11 (42%) grey-level co-occurrence RFs and five (42%) grey-level run length RFs showed acceptable reliability. Our study suggests that optimization of SNR, exclusion of outliers, and application of relevant quantization range and bin number should be performed to ensure the robustness of radiomics studies assessing tumor heterogeneity.
Silent circulation of dengue virus in Aedes albopictus (Diptera: Culicidae) resulting from natural vertical transmission
Authors: Ferreira-de-Lima Victor Henrique , Andrade Pâmela dos Santos , Thomazelli Luciano Matsumiya , Marrelli Mauro Toledo , Urbinatti Paulo Roberto , Almeida Rosa Maria Marques de Sá , Lima-Camara Tamara Nunes 
Published: March 2020

AbstractVertical transmission in Aedes aegypti and Aedes albopictus is considered a maintenance mechanism for dengue virus (DENV) during unfavorable conditions and may be implicated in dengue outbreaks. Since DENV infection dynamics vary among wild-type viruses and vector populations, vertical transmission rates can also vary between regions. However, even though São Paulo is the most populous city in the Americas and has experienced major dengue epidemics, natural vertical transmission had never been detected in this area before. Here we confirm and describe for the first time natural vertical transmission of DENV-3 in two pools of male Ae. albopictus from the city of São Paulo. The detection of DENV-3 in years when no human autochthonous cases of this serotype were recorded suggests that silent circulation of DENV-3 is occurring and indicates that green areas may be maintaining serotypes that are not circulating in the human population, possibly by a vertical transmission mechanism.
Multi-target immunofluorescence by separation of antibody cross-labelling via spectral-FLIM-FRET
Authors: Rohilla Sumeet , Krämer Benedikt , Koberling Felix , Gregor Ingo , Hocke Andreas C. 
Published: March 2020

AbstractIn biomedical research, indirect immunofluorescence labelling by use of primary and secondary antibodies is central for revealing the spatial distribution of multiple cellular antigens. However, labelling is regularly restricted to few antigens since species variation of primary and corresponding secondary antibodies is limited bearing the risk of unspecific cross-labelling. Here, we introduce a novel microscopic procedure for leveraging undesirable cross-labelling effects among secondary antibodies thereby increasing the number of fluorophore channels. Under cross-labelling conditions, commonly used fluorophores change chemical-physical properties by ‘Förster resonance energy transfer’ leading to defined changes in spectral emission and lifetime decay. By use of spectral fluorescence lifetime imaging and pattern-matching, we demonstrate precise separation of cross-labelled cellular antigens where conventional imaging completely fails. Consequently, this undesired effect serves for an innovative imaging procedure to separate critical antigens where antibody species variation is limited and allows for multi-target labelling by attribution of new fluorophore cross-labelling channels.
Theoretical investigation of the Humphreys–Davidson limit at high and low metallicity
Authors: Higgins Erin R. , Vink Jorick S. 
Published: March 2020

Context. Current massive star evolution grids are not able to simultaneously reproduce the empirical upper luminosity limit of red supergiants, the Humphrey–Davidson (HD) limit, nor the blue-to-red (B/R) supergiant ratio at high and low metallicity. Although previous studies have shown that the treatment of convection and semi-convection plays a role in the post-main-sequence (MS) evolution to blue or red supergiants (RSGs), a unified treatment for all metallicities has not been achieved so far.
Aims. We focus on developing a better understanding of what drives massive star evolution to blue and red supergiant phases, with the ultimate aim of reproducing the HD limit at varied metallicities. We discuss the consequences of classifying B and R in the B/R ratio and clarify what is required to quantify a relatable theoretical B/R ratio for comparison with observations.
Methods. For solar, Large Magellanic Cloud (50% solar), and Small Magellanic Cloud (20% solar) metallicities, we develop eight grids of MESA models for the mass range 20–60 M⊙ to probe the effect of semi-convection and overshooting on the core helium-burning phase. We compare rotating and non-rotating models with efficient (αsemi = 100) and inefficient semi-convection (αsemi = 0.1), with high and low amounts of core overshooting (αov of 0.1 or 0.5). The red and blue supergiant evolutionary phases are investigated by comparing the fraction of core He-burning lifetimes spent in each phase for a range of masses and metallicities.
Results. We find that the extension of the convective core by overshooting αov = 0.5 has an effect on the post-MS evolution that can disable semi-convection, leading to more RSGs, but a lack of BSGs. We therefore implement αov = 0.1, which switches on semi-convective mixing, but for standard αsemi = 1 would result in an HD limit that is higher than observed at low Z (Large and Small Magellanic Clouds). Therefore, we need to implement very efficient semi-convection of αsemi = 100, which reproduces the HD limit at log L/L⊙ ∼ 5.5 for the Magellanic Clouds while simultaneously reproducing the Galactic HD limit of log L/L⊙ ∼ 5.8 naturally. The effect of semi-convection is not active at high metallicities because the envelope structure is depleted by strong mass loss such that semi-convective regions could not form.
Conclusions. Metallicity-dependent mass loss plays an indirect, yet decisive role in setting the HD limit as a function of Z. For a combination of efficient semi-convection and low overshooting with standard Ṁ(Z), we find a natural HD limit at all metallicities.
Gallensteine – interdisziplinäre Behandlung
Authors: Scherber Philipp Robert , Zúniga Silvia Eugenia , Glanemann Matthias , Lammert Frank 
Published: March 2020

AbstractGallstones develop in the gallbladder or the bile ducts. According to their chemical composition, gallstones can be divided into cholesterol stones, which are common, and the rare bile pigment stones. Altogether, up to 20 % of all adults develop gallstones and more than 20 % of them symptoms or complications. Female sex, age, pregnancy, physical inactivity, obesity, overnutrition and genetic factors such as ABCB4 deficiency of the hepatic lecithin transporter are kown risk factors for gallstone formation. In about one half of all patients biliary symptoms precede the three common and potentially life-threatening complications (acute cholecystitis, acute cholangitis and biliary pancreatitis). Although our knowledge about the genetics and pathophysiology of gallstones has improved, current treatment algorithms are predominantly invasive (ERC and surgery). Thus, better strategies are needed to prevent the formation of gallstones in general.
Autoimmune cholestatische Lebererkrankungen
Authors: Mayer Lena Sophie , Käser Rafael , Böttler Tobias 
Published: March 2020

AbstractPrimary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are rare, autoimmune mediated cholestatic liver diseases. Other auto-immune diseases are often associated with PBC and PSC, and inflammatory bowel disease is present in the majority of PSC patients. In the course of disease, chronic inflammation in the liver leads to fibrotic restructuring and ultimately cirrhosis. The diagnosis of PBC is confirmed serologically and PSC is diagnosed via cholangiography, whereas MRCP is preferred over ERCP. For PBC, the first line therapy is ursodeoxycholic acid (UDCA). Prognosis is strongly dependent on the response to UDCA. The only approved second line therapy is obeticholic acid (OCA). Alternatively, Budesonide or Fibrates are often used off-label. In the management of PSC, prevention and adequate treatment of bacterial cholangitis play a major role. For both PBC and PSC novel treatments are currently being tested in clinical trials. Disease management should address compromising symptoms like pruritus and sicca as well as complications due to maldigestion and concomitant autoimmune diseases. The only curative treatment available is liver transplantation and should be considered at a MELD score of 15.
FUNGAL PROFILE OF INFECTIOUS KERATITIS IN A TERTIARY CARE HOSPITAL - OUR EXPERIENCE
Authors: H. Sanjeev , K. Karnaker Vimal , Vijay Pai , B. Pai Asha K. , Rekha Rai , S. Krishnaprasad M. 
Published: March 2020

AbstractInfectious keratitis world wide are a leading cause of ocular morbidity and blindness. A large number of filamentous fungi, Yeasts and Zygomycetes have been incriminated as the causative agent of mycotic keratitis. Early diagnosis and treatment is important in preventing complications like corneal perforation, scleral spread and endopthalmitis. The present study was conducted to elucidate the epidemiological features of mycotic keratitis and study the fungal profile of mycotic keratitis of patients attending our hospital, which is situated on the coastal area of Karnataka.A total of 127 patients with infectious keratitis were investigated between January 2009 to June 2010. Corneal scraping was obtained from 127 patients under aseptic precaution. The scraping was subjected to 10% KOH wet mount, Gram's staining and culture. Of the total 127 patients suspected of having infectious keratitis, 44 (34.65%) were found to be positive for fungal aetiology. Of these, 40(90.90%) cases were positive on direct microscopy for fungal elements and 26(59.09%) cases showed growth on culture after incubation for 2-8 days. In 14 (31.81%) cases, the culture was found to be sterile despite positive direct microscopic findings, but the results were consistent with clinical findings. Positive culture was obtained in 4(09.09%) cases where direct microscopy was found to be negative. The commonest fungi isolated were Aspergillus species (61.5%)Mycotic keratitis continues to be an important cause of ocular morbidity, predominantly among rural population. Prompt diagnosis and early institution of antifungal therapy may limit the ocular morbidity and the sequelae of infectious keratitis. As the manifestation of mycotic keratitis is often confusing, a high degree of suspicion with sound knowledge of predisposing factors and microbiological confirmation is very essential to initiate appropriate therapy.