bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hPSC-based platform to discover gene-environment interactions that impact human β-cell and dopamine neuron survival
Authors: Zhou Ting , Kim Tae Wan , Chong Chi Nok , Tan Lei , Amin Sadaf , Sadat Badieyan Zohreh , Mukherjee Suranjit , Ghazizadeh Zaniar , Zeng Hui , Guo Min , Crespo Miguel , Zhang Tuo , Kenyon Reyn , Robinson Christopher L. , Apostolou Effie , Wang Hui , Xiang Jenny Zhaoying , Evans Todd , Studer Lorenz , Chen Shuibing 
Published: November 2018

AbstractCommon disorders, including diabetes and Parkinson’s disease, are caused by a combination of environmental factors and genetic susceptibility. However, defining the mechanisms underlying gene-environment interactions has been challenging due to the lack of a suitable experimental platform. Using pancreatic β-like cells derived from human pluripotent stem cells (hPSCs), we discovered that a commonly used pesticide, propargite, induces pancreatic β-cell death, a pathological hallmark of diabetes. Screening a panel of diverse hPSC-derived cell types we extended this observation to a similar susceptibility in midbrain dopamine neurons, a cell type affected in Parkinson’s disease. We assessed gene-environment interactions using isogenic hPSC lines for genetic variants associated with diabetes and Parkinson’s disease. We found GSTT1−/− pancreatic β-like cells and dopamine neurons were both hypersensitive to propargite-induced cell death. Our study identifies an environmental chemical that contributes to human β-cell and dopamine neuron loss and validates a novel hPSC-based platform for determining gene-environment interactions.
Optogenetic dissection of Rac1 and Cdc42 gradient shaping
Authors: de Beco S. , Vaidžiulytė K. , Manzi J. , Dalier F. , di Federico F. , Cornilleau G. , Dahan M. , Coppey M. 
Published: November 2018

AbstractDuring cell migration, Rho GTPases spontaneously form spatial gradients that define the front and back of cells. At the front, active Cdc42 forms a steep gradient whereas active Rac1 forms a more extended pattern peaking a few microns away. What are the mechanisms shaping these gradients, and what is the functional role of the shape of these gradients? Here we report, using a combination of optogenetics and micropatterning, that Cdc42 and Rac1 gradients are set by spatial patterns of activators and deactivators and not directly by transport mechanisms. Cdc42 simply follows the distribution of Guanine nucleotide Exchange Factors, whereas Rac1 shaping requires the activity of a GTPase-Activating Protein, β2-chimaerin, which is sharply localized at the tip of the cell through feedbacks from Cdc42 and Rac1. Functionally, the spatial extent of Rho GTPases gradients governs cell migration, a sharp Cdc42 gradient maximizes directionality while an extended Rac1 gradient controls the speed.
Serotonin signals through a gut-liver axis to regulate hepatic steatosis
Authors: Choi Wonsuk , Namkung Jun , Hwang Inseon , Kim Hyeongseok , Lim Ajin , Park Hye Jung , Lee Hye Won , Han Kwang-Hyub , Park Seongyeol , Jeong Ji-Seon , Bang Geul , Kim Young Hwan , Yadav Vijay K. , Karsenty Gerard , Ju Young Seok , Choi Chan , Suh Jae Myoung , Park Jun Yong , Park Sangkyu , Kim Hail 
Published: November 2018

AbstractNonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.
Systematic review of association between critical errors in inhalation and health outcomes in asthma and COPD
Authors: Kocks Janwillem W. H. , Chrystyn Henry , van der Palen Job , Thomas Mike , Yates Louisa , Landis Sarah H. , Driessen Maurice T. , Gokhale Mugdha , Sharma Raj , Molimard Mathieu 
Published: November 2018

AbstractInhaled medications are the cornerstone of treatment and management of asthma and COPD. However, inhaler device errors are common among patients and have been linked with reduced symptom control, an increased risk of exacerbations, and increased healthcare utilisation. These observations have prompted GINA (Global INitiative for Asthma) and GOLD (Global initiative for chronic Obstructive Lung Disease) to recommend regular assessment of inhaler technique in a bid to improve therapeutic outcomes. To better define the relationship between device errors and health outcomes (clinical outcomes, quality of life, and healthcare utilisation) in asthma and COPD, we conducted a systematic review of the literature, with a particular focus on the methods used to assess the relationship between device errors and outcomes. Sixteen studies were identified (12 in patients with asthma, one in patients with COPD, and three in both asthma and COPD) with varying study designs, endpoints, and patient populations. Most of the studies reported that inhalation errors were associated with worse disease outcomes in patients with asthma or COPD. Patients who had a reduction in errors over time had improved outcomes. These findings suggest that time invested by healthcare professionals is vital to improving inhalation technique in asthma and COPD patients to improve health outcomes.
Computational Imaging Prediction of Starburst-Effect Diffraction Spikes
Authors: Lendermann Markus , Tan Joel Shi Quan , Koh Jin Ming , Cheong Kang Hao 
Published: November 2018

AbstractWhen imaging bright light sources, rays of light emanating from their centres are commonly observed; this ubiquitous phenomenon is known as the starburst effect. The prediction and characterization of starburst patterns formed by extended sources have been neglected to date. In the present study, we propose a novel trichromatic computational framework to calculate the image of a scene viewed through an imaging system with arbitrary focus and aperture geometry. Diffractive light transport, imaging sensor behaviour, and implicit image adjustments typical in modern imaging equipment are modelled. Characterization methods for key optical parameters of imaging systems are also examined. Extensive comparisons between theoretical and experimental results reveal excellent prediction quality for both focused and defocused systems.
Skyrmionium – high velocity without the skyrmion Hall effect
Authors: Kolesnikov Alexander G. , Stebliy Maksim E. , Samardak Alexander S. , Ognev Alexey V. 
Published: November 2018

AbstractThe lateral motion of a magnetic skyrmion, arising because of the skyrmion Hall effect, imposes a number of restrictions on the use of this spin state in the racetrack memory. A skyrmionium is a more promising spin texture for memory applications, since it has zero total topological charge and propagates strictly along a nanotrack. Here, the stability of the skyrmionium, as well as the dependence of its size on the magnetic parameters, such as the Dzyaloshinskii–Moriya interaction and perpendicular magnetic anisotropy, are studied by means of micromagnetic simulations. We propose an advanced method for the skyrmionium nucleation due to a local enhancement of the spin Hall effect. The stability of the skyrmionium being in motion under the action of the spin polarized current is analyzed.
Surface mechanomyography and electromyography provide non-invasive indices of inspiratory muscle force and activation in healthy subjects
Authors: Lozano-García Manuel , Sarlabous Leonardo , Moxham John , Rafferty Gerrard F. , Torres Abel , Jané Raimon , Jolley Caroline J. 
Published: November 2018

AbstractThe current gold standard assessment of human inspiratory muscle function involves using invasive measures of transdiaphragmatic pressure (Pdi) or crural diaphragm electromyography (oesEMGdi). Mechanomyography is a non-invasive measure of muscle vibration associated with muscle contraction. Surface electromyogram and mechanomyogram, recorded transcutaneously using sensors placed over the lower intercostal spaces (sEMGlic and sMMGlic respectively), have been proposed to provide non-invasive indices of inspiratory muscle activation, but have not been directly compared to gold standard Pdi and oesEMGdi measures during voluntary respiratory manoeuvres. To validate the non-invasive techniques, the relationships between Pdi and sMMGlic, and between oesEMGdi and sEMGlic were measured simultaneously in 12 healthy subjects during an incremental inspiratory threshold loading protocol. Myographic signals were analysed using fixed sample entropy (fSampEn), which is less influenced by cardiac artefacts than conventional root mean square. Strong correlations were observed between: mean Pdi and mean fSampEn |sMMGlic| (left, 0.76; right, 0.81), the time-integrals of the Pdi and fSampEn |sMMGlic| (left, 0.78; right, 0.83), and mean fSampEn oesEMGdi and mean fSampEn sEMGlic (left, 0.84; right, 0.83). These findings suggest that sMMGlic and sEMGlic could provide useful non-invasive alternatives to Pdi and oesEMGdi for the assessment of inspiratory muscle function in health and disease.
Identification of Two Mannosyltransferases Contributing to Biosynthesis of the Fungal-type Galactomannan α-Core-Mannan Structure in Aspergillus fumigatus
Authors: Onoue Takuya , Tanaka Yutaka , Hagiwara Daisuke , Ekino Keisuke , Watanabe Akira , Ohta Kazuyoshi , Kamei Katsuhiko , Shibata Nobuyuki , Goto Masatoshi , Oka Takuji 
Published: November 2018

AbstractFungal-type galactomannan (FTGM) is a polysaccharide composed of α-(1 → 2)-/α-(1 → 6)-mannosyl and β-(1 → 5)-/β-(1 → 6)-galactofuranosyl residues located at the outer cell wall of the human pathogenic fungus Aspergillus fumigatus. FTGM contains a linear α-mannan structure called core-mannan composed of 9 or 10 α-(1 → 2)-mannotetraose units jointed by α-(1 → 6)-linkages. However, the enzymes involved in core-mannan biosynthesis remain unknown. We speculated that two putative α-1,2-mannosyltransferase genes in A. fumigatus, Afu5g02740/AFUB_051270 (here termed core-mannan synthase A [CmsA]) and Afu5g12160/AFUB_059750 (CmsB) are involved in FTGM core-mannan biosynthesis. We constructed recombinant proteins for CmsA and detected robust mannosyltransferase activity using the chemically synthesized substrate p-nitrophenyl α-d-mannopyranoside as an acceptor. Analyses of CmsA enzymatic product revealed that CmsA possesses the capacity to transfer a mannopyranoside to the C-2 position of α-mannose. CmsA could also transfer a mannose residue to α-(1 → 2)-mannobiose and α-(1 → 6)-mannobiose and showed a 31-fold higher specific activity toward α-(1 → 6)-mannobiose than toward α-(1 → 2)-mannobiose. Proton nuclear magnetic resonance (1H-NMR) spectroscopy and gel filtration chromatography of isolated FTGM revealed that core-mannan structures were drastically altered and shortened in disruptant A. fumigatus strains ∆cmsA, ∆cmsB, and ∆cmsA∆cmsB. Disruption of cmsA or cmsB resulted in severely repressed hyphal extension, abnormal branching hyphae, formation of a balloon structure in hyphae, and decreased conidia formation. The normal wild type core-mannan structure and developmental phenotype were restored by the complementation of cmsA and cmsB in the corresponding disruptant strains. These findings indicate that both CmsA, an α-1,2-mannosyltransferase, and CmsB, a putative mannosyltransferase, are involved in FTGM biosynthesis.
Tear Proteins Calcium binding protein A4 (S100A4) and Prolactin Induced Protein (PIP) are Potential Biomarkers for Thyroid Eye Disease
Authors: Chng Chiaw-Ling , Seah Lay Leng , Yang Morgan , Shen Sunny Yu , Koh Siew Kwan , Gao Yan , Deng Lu , Tong Louis , Beuerman Roger Wilmer , Zhou Lei 
Published: November 2018

AbstractThere are no reliable biomarkers to predict thyroid eye disease (TED) in patients with autoimmune thyroid disease (AITD) currently. Several evidences support the involvement of the lacrimal gland in TED. The aim of our study was to quantitatively correlate the changes in tear protein profile with increasing severity of TED. Tear samples were collected from four groups of patients; AITD without TED (AITD), AITD with mild TED (mild TED), AITD with severe TED (severe TED) and normal controls. A total of 72 patients were recruited for the study. In discovery phase, isobaric tags for relative and absolute quantification (iTRAQ) 4-plex was used for quantitative proteomics analysis. For verification of results from discovery phase, sequential window acquisition of all theoretical fragment ion spectra (SWATH) was used to analyze an independent cohort from normal controls, AITD, mild TED and severe TED. Two proteins, S100A4 and PIP showed consistent dysregulation trends in the discovery and validation phase experiments. Our study demonstrated the differences in tear proteome across the spectrum of different severity and activity of TED in patients with AITD. Two tear proteins, S100A4 and PIP may serve as potential biomarkers to predict progression to severe TED in patients with AITD.
Influences of vertical differences in population emigration on mountainous vegetation greenness: A case study in the Taihang Mountains
Authors: Li Wei , Tan Minghong 
Published: November 2018

AbstractWith the rapid advance of urbanization, rural population emigration has become a key factor that affects the man-land relationship in China’s mountainous areas and may have a huge impact on ecological restoration. This study used the NDVI in the growing seasons to analyze the variation trend of vegetation greenness at different elevations in the Taihang Mountains during 2000–2010, employing trend analysis method. Then, we selected 990 samples, each of which was a circular area with a radius of 3 km. On this basis, we quantitatively analyzed the contribution degree of population emigration to this variation trend after eliminating the influences of precipitation, temperature, and other factors. The results showed that rural population emigration was significant in the Taihang Mountains in the past 10 years, with a rural population emigration rate of up to 16.3%; The vegetation in the Taihang Mountains presented a trend of overall improvement, but local deterioration; The results of the regression analysis showed that population emigration had significantly impacts on vegetation greenness at 1% significance level and 1% of population emigration can increase the NDVI variation trend by 0.06%. Furthermore, the impact gradually weakened with increasing elevation.
Low level DUX4 expression disrupts myogenesis through deregulation of myogenic gene expression
Authors: Bosnakovski Darko , Gearhart Micah D. , Toso Erik A. , Ener Elizabeth T. , Choi Si Ho , Kyba Michael 
Published: November 2018

AbstractLoss of silencing of the DUX4 gene on chromosome 4 causes facioscapulohumeral muscular dystrophy. While high level DUX4 expression induces apoptosis, the effects of low level DUX4 expression on human myogenic cells are not well understood. Low levels and sporadic expression of DUX4 have been reported in FSHD biopsy samples and myoblast cultures. Here, we show that a large set of human myogenic genes is rapidly deregulated by DUX4, including MYOD1 and MYF5, which are efficiently repressed even by low, non-toxic levels of DUX4. Human myoblasts modified to express low nontoxic levels of DUX4 were significantly impaired from differentiating into myotubes in vitro. Surprisingly, inhibition of differentiation does not require the transcriptional activation domain, thus is likely a feature of all mammalian DUX genes. DUX4 does not bind near the MYF5 gene, but has a prominent ChIP-seq peak within the MYF5 −118 kb enhancer. We find that when DUX4 binds at this site, it directs enhancer activity towards a nearby transcriptional start site for a noncoding nonfunctional RNA we name DIME (DUX4-induced MYF5 enhancer) transcript. These data highlight the anti-myogenic properties of DUX4 in human myogenic progenitor cells, and provide an example of enhancer disruption in the downregulation of MYF5.
In vitro neural networks minimise variational free energy
Authors: Isomura Takuya , Friston Karl 
Published: November 2018

AbstractIn this work, we address the neuronal encoding problem from a Bayesian perspective. Specifically, we ask whether neuronal responses in an in vitro neuronal network are consistent with ideal Bayesian observer responses under the free energy principle. In brief, we stimulated an in vitro cortical cell culture with stimulus trains that had a known statistical structure. We then asked whether recorded neuronal responses were consistent with variational message passing based upon free energy minimisation (i.e., evidence maximisation). Effectively, this required us to solve two problems: first, we had to formulate the Bayes-optimal encoding of the causes or sources of sensory stimulation, and then show that these idealised responses could account for observed electrophysiological responses. We describe a simulation of an optimal neural network (i.e., the ideal Bayesian neural code) and then consider the mapping from idealised in silico responses to recorded in vitro responses. Our objective was to find evidence for functional specialisation and segregation in the in vitro neural network that reproduced in silico learning via free energy minimisation. Finally, we combined the in vitro and in silico results to characterise learning in terms of trajectories in a variational information plane of accuracy and complexity.
Genome-wide analysis of Streptococcus pneumoniae serogroup 19 in the decade after the introduction of pneumococcal conjugate vaccines in Australia
Authors: Rockett Rebecca J. , Oftadeh Shahin , Bachmann Nathan L. , Timms Verlaine J. , Kong Fanrong , Gilbert Gwendolyn L. , Sintchenko Vitali 
Published: November 2018

AbstractThe decline in invasive pneumococcal disease (IPD), following the introduction of the 7-valent pneumococcal conjugate vaccination (PCV-7), was tempered by emergence of non-vaccine serotypes, particularly 19A. In Australia, three years after PCV-7 was replaced by PCV-13, containing 19A and 19F antigens, serogroup 19 was still a prominent cause of IPD in children under five. In this study we examined the evolution of serogroup 19 before and after introduction of paediatric vaccines in New South Wales (NSW), Australia. Genomes of 124 serogroup 19 IPD isolates collected before (2004) and after introduction of PCV-7 (2008) and PCV-13 (2014), from children under five in NSW, were analysed. Eleven core genome sequence clusters (cgSC) and 35 multilocus sequence types (ST) were identified. The majority (78/124) of the isolates belonged to four cgSCs: cgSC7 (ST199), cgSC11 (ST320), cgSC8 (ST63) and cgSC9 (ST2345). ST63 and ST2345 were exclusively serotype 19A and accounted for its predominantly intermediate penicillin resistance; these two clusters first appeared in 2008 and largely disappeared after introduction of PCV-13. Serogroup 19 was responsible for the highest proportion of vaccine failures in NSW. Relatively low immunogenicity of serogroup 19 antigens and Australia’s three-dose vaccine schedule could affect the population dynamics of this serogroup.
Identification of key influence factors and an empirical formula for spring snowmelt-runoff: A case study in mid-temperate zone of northeast China
Authors: Tian Lin , Li Hongyan , Li Fengping , Li Xiubin , Du Xinqiang , Ye Xueyan 
Published: November 2018

AbstractBecause of the unique climate characteristics, the runoff law in mid-temperate zone is very different from other regions in spring. Accurate runoff simulation and forecasting is of great importance to spring flood control and efficient use of water resources. Baishan reservoir is located in the upper Second Songhua River Basin in Northeast China, where snowmelt is an important source of runoff that contributes to the water supply. This study utilized long-term hydrometeorological data, in the contributing area of Bashan reservoir, to investigate factors and time-lag effects on spring snowmelt and to establish a snowmelt-runoff model. Daily precipitation, temperature, and wind data were collected from three meteorological stations in this region from 1987–2016. Daily runoff into the Baishan reservoir was selected for the same period. The snowmelt period was identified from March 23 to May 4 through baseflow segmentation with the Eckhardt recursive digital filtering method combined with statistical analyses. A global sensitivity analysis, based on the back propagation neural network method, was used to identify daily radiation, wind speed, mean temperature, and precipitation as the main factors affecting snowmelt runoff. Daily radiation, precipitation, and mean temperature factors had a two-day lag effect. Based on these factors, an empirical snowmelt runoff model was established by genetic algorithm (GAS) to estimate the snowmelt runoff in this area. The model showed an acceptable performance with coefficient of determination (R2) of 73.6%, relative error (Re) of 25.10%, and Nash-Sutcliffe efficiency coefficient (NSE) of 66.2% in the calibration period of 1987–2010, while reasonable performance with R2 of 62.3%, Re of 27.2%, and NSE of 46.0% was also achieved during the 2011–2016 validation period.
Increased susceptibility to cortical spreading depression and epileptiform activity in a mouse model for FHM2
Authors: Kros Lieke , Lykke-Hartmann Karin , Khodakhah Kamran 
Published: November 2018

AbstractMigraine is a highly prevalent, debilitating, episodic headache disorder affecting roughly 15% of the population. Familial hemiplegic migraine type 2 (FHM2) is a rare subtype of migraine caused by mutations in the ATP1A2 gene, encoding the α2 isoform of the Na+/K+-ATPase, predominantly expressed in astrocytes. Differential comorbidities such as epilepsy and psychiatric disorders manifest in patients. Using a mouse model harboring the G301R disease-mutation in the α2 isoform, we set to unravel whether α2+/G301R mice show an increased susceptibility for epilepsy and cortical spreading depression (CSD). We performed in vivo experiments involving cortical application of KCl in awake head-restrained male and female mice of different age groups (adult and aged). Interestingly, α2+/G301R mice indeed showed an increased susceptibility to both CSD and epileptiform activity, closely replicating symptoms in FHM2 patients harboring the G301R and other FHM2-causing mutations. Additionally, this epileptiform activity was superimposed on CSDs. The age-related alteration towards CSD indicates the influence of female sex hormones on migraine pathophysiology. Therefore, the FHM2, α2+/G301R mouse model can be utilized to broaden our understanding of generalized epilepsy and comorbidity hereof in migraine, and may be utilized toward future selection of possible treatment options for migraine.