bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purkinje cell number-correlated cerebrocerebellar circuit anomaly in the valproate model of autism
Authors: Spisák Tamás , Román Viktor , Papp Edit , Kedves Rita , Sághy Katalin , Csölle Cecília Katalin , Varga Anita , Gajári Dávid , Nyitrai Gabriella , Spisák Zsófia , Kincses Zsigmond Tamás , Lévay György , Lendvai Balázs , Czurkó András 
Published: June 2019

AbstractWhile cerebellar alterations may play a crucial role in the development of core autism spectrum disorder (ASD) symptoms, their pathophysiology on the function of cerebrocerebellar circuit loops is largely unknown. We combined multimodal MRI (9.4 T) brain assessment of the prenatal rat valproate (VPA) model and correlated immunohistological analysis of the cerebellar Purkinje cell number to address this question. We hypothesized that a suitable functional MRI (fMRI) paradigm might show some altered activity related to disrupted cerebrocerebellar information processing. Two doses of maternal VPA (400 and 600 mg/kg, s.c.) were used. The higher VPA dose induced 3% smaller whole brain volume, the lower dose induced 2% smaller whole brain volume and additionally a focal gray matter density decrease in the cerebellum and brainstem. Increased cortical BOLD responses to whisker stimulation were detected in both VPA groups, but it was more pronounced and extended to cerebellar regions in the 400 mg/kg VPA group. Immunohistological analysis revealed a decreased number of Purkinje cells in both VPA groups. In a detailed analysis, we revealed that the Purkinje cell number interacts with the cerebral BOLD response distinctively in the two VPA groups that highlights atypical function of the cerebrocerebellar circuit loops with potential translational value as an ASD biomarker.
Automatic classification of IgA endomysial antibody test for celiac disease: a new method deploying machine learning
Authors: Caetano dos Santos Florentino Luciano , Michalek Irmina Maria , Laurila Kaija , Kaukinen Katri , Hyttinen Jari , Lindfors Katri 
Published: June 2019

AbstractWidespread use of endomysial autoantibody (EmA) test in diagnostics of celiac disease is limited due to its subjectivity and its requirement of an expert evaluator. The study aimed to determine whether machine learning can be applied to create a new observer-independent method of automatic assessment and classification of the EmA test for celiac disease. The study material comprised of 2597 high-quality IgA-class EmA images collected in 2017–2018. According to standard procedure, highly-experienced professional classified samples into the following four classes: I - positive, II - negative, III - IgA deficient, and IV - equivocal. Machine learning was deployed to create a classification model. The sensitivity and specificity of the model were 82.84% and 99.40%, respectively. The accuracy was 96.80%. The classification error was 3.20%. The area under the curve was 99.67%, 99.61%, 100%, and 99.89%, for I, II, III, and IV class, respectively. The mean assessment time per image was 16.11 seconds. This is the first study deploying machine learning for the automatic classification of IgA-class EmA test for celiac disease. The results indicate that using machine learning enables quick and precise EmA test analysis that can be further developed to simplify EmA analysis.
A comprehensive, multiscale framework for evaluation of arrhythmias arising from cell therapy in the whole post-myocardial infarcted heart
Authors: Yu Joseph K. , Franceschi William , Huang Qinwen , Pashakhanloo Farhad , Boyle Patrick M. , Trayanova Natalia A. 
Published: June 2019

AbstractDirect remuscularization approaches to cell-based heart repair seek to restore ventricular contractility following myocardial infarction (MI) by introducing new cardiomyocytes (CMs) to replace lost or injured ones. However, despite promising improvements in cardiac function, high incidences of ventricular arrhythmias have been observed in animal models of MI injected with pluripotent stem cell-derived cardiomyocytes (PSC-CMs). The mechanisms of arrhythmogenesis remain unclear. Here, we present a comprehensive framework for computational modeling of direct remuscularization approaches to cell therapy. Our multiscale 3D whole-heart modeling framework integrates realistic representations of cell delivery and transdifferentiation therapy modalities as well as representation of spatial distributions of engrafted cells, enabling simulation of clinical therapy and the prediction of emergent electrophysiological behavior and arrhythmogenensis. We employ this framework to explore how varying parameters of cell delivery and transdifferentiation could result in three mechanisms of arrhythmogenesis: focal ectopy, heart block, and reentry.
The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans
Authors: Palmer-Brown William , Miranda-CasoLuengo Raúl , Wolfe Kenneth H. , Byrne Kevin P. , Murphy Cormac D. 
Published: June 2019

AbstractThe fungus Cunninghamella elegans is recognised as a microbial model of mammalian drug metabolism owing to its ability to catabolise xenobiotic compounds in an analogous fashion to animals. Its ability to produce phase I (oxidative) metabolites of drugs is associated with cytochrome P450 (CYP) activity; however, almost nothing is known about these enzymes in the fungus. In this paper we report the in silico analysis of the genome sequence of C. elegans B9769, which contains 32 genes putatively coding for CYPs. Based on their predicted amino acid sequences these were classified as belonging to CYP509, 5203, 5208, 5313, 5210, 61 and 51 families. Reverse transcription-quantitative PCR revealed that the gene coding for CYP5313D1 was significantly upregulated when C. elegans DSM1908 was cultivated in sabouraud dextrose in contrast to its expression in cells grown in Roswell Park Memorial Institute medium. This corresponded to the fungus’ xenobiotic biotransformation ability when grown in the two media. Heterologous expression of cyp5313D1 in Pichia pastoris resulted in a recombinant strain that biotransformed flurbiprofen to 4′-hydroxyflurbiprofen, the same metabolite generated by C. elegans cultures. This is the first report of a xenobiotic-biotransforming CYP from this biotechnologically important fungus.
A 3-D Projection Model for X-ray Dark-field Imaging
Authors: Felsner Lina , Hu Shiyang , Maier Andreas , Bopp Johannes , Ludwig Veronika , Anton Gisela , Riess Christian 
Published: June 2019

AbstractThe X-ray dark-field signal can be measured with a grating-based Talbot-Lau interferometer. It measures small angle scattering of micrometer-sized oriented structures. Interestingly, the signal is a function not only of the material, but also of the relative orientation of the sample, the X-ray beam direction, and the direction of the interferometer sensitivity. This property is very interesting for potential tomographically reconstructing structures below the imaging resolution. However, tomographic reconstruction itself is a substantial challenge. A key step of the reconstruction algorithm is the inversion of a forward projection model. In this work, we propose a very general 3-D projection model. We derive the projection model under the assumption that the observed scatter distribution has a Gaussian shape. We theoretically show the consistency of our model with existing, more constrained 2-D models. Furthermore, we experimentally show the compatibility of our model with simulations and real dark-field measurements. We believe that this 3-D projection model is an important step towards more flexible trajectories and, by extension, dark-field imaging protocols that are much better applicable in practice.
Production of Fungal Phytases from Agroindustrial Byproducts for Pig Diets
Authors: Pires Elizabeth Bárbara Epalanga , de Freitas Anderson Junior , Souza Fernanda França e , Salgado Rafael Locatelli , Guimarães Valéria Monteze , Pereira Francisco Alves , Eller Monique Renon 
Published: June 2019

AbstractThe application of phytases for animal feed in developing countries is limited due to the high cost of these enzymes, determined by the importation fees and the expensive substrates used for their production. In this work, we have used agroindustrial byproducts for the production of extracts containing phytases, which were accessed for their stability focusing on the conditions found in the gastrointestinal tract of pigs. The fungus Acremonim zeae presented higher phytase production in medium containing cornmeal, while the yeast Kluyveromyces marxianus produced 10-fold more phytase when cultivated on rice bran. Process optimization increased the difference in productivity to more than 300 fold. The phytase from A. zeae was thermostable, with higher activity at neutral pH and 50 °C, but was inhibited at pH 2.5 and by various ions. The phytase activity in the K. marxianus extract was stable at a wide range of conditions, which indicates the presence of at least two enzymes. As far as we know, this manuscript describes for the first time the phytase production and the characteristics of the extracts produced by both these microbial species. These enzymes could be produced at low cost and have potential to replace enzymes currently imported for this purpose.
Conformational changes influence clogging behavior of micrometer-sized microgels in idealized multiple constrictions
Authors: Bouhid de Aguiar Izabella , Meireles Martine , Bouchoux Antoine , Schroën Karin 
Published: June 2019

AbstractClogging of porous media by soft particles has become a subject of extensive research in the last years and the understanding of the clogging mechanisms is of great importance for process optimization. The rise in the utilization of microfluidic devices brought the possibility to simulate membrane filtration and perform in situ observations of the pore clogging mechanisms with the aid of high speed cameras. In this work, we use microfluidic devices composed by an array of parallel channels to observe the clogging behavior of micrometer sized microgels. It is important to note that the microgels are larger than the pores/constrictions. We quantify the clog propensity in relation to the clogging position and particle size and find that the majority of the microgels clog at the first constriction independently of particle size and constriction entrance angle. We also quantify the variations in shape and volume (2D projection) of the microgels in relation to particle size and constriction entrance angle. We find that the degree of deformation increases with particle size and is dependent of constriction entrance angle, whereas, changes in volume do not depend on entrance angle.
Recent changes in the South America low-level jet
Authors: Jones Charles 
Published: June 2019

AbstractThe South America Low-level Jet (SALLJ) is a climatological feature with a critical role in the spatiotemporal distribution of precipitation in South America. While previous studies have focused on the mechanisms and variability of the SALLJ in the central Andes (i.e., southeast Peru, Bolivia, and Paraguay), the occurrence of the low-level jet in the eastern slopes of the northern Andes (i.e., northeast Peru, Colombia, and Venezuela) and its linkages to the central region have not been previously explored. This study shows that the SALLJ in the northern branch exceeds 10 m s−1 during September–February and the frequency can be as high as in the central region. Moreover, the SALLJ can occur simultaneously or separately in both regions. When the SALLJ is active only in the northern branch, wind speeds are very low from Bolivia towards southeast South America (SESA) and precipitation is significantly reduced (1–4 mm day−1) from climatology. In contrast, precipitation increases over eastern Bolivia by 2–4 mm day−1. Composites suggest that the SALLJ northern branch is forced by a large-scale circulation pattern with the enhancement of the North Atlantic Subtropical High driving northeasterly winds over the northern Andes. Further analysis shows that the frequency and intensity of the SALLJ in the northern Andes has substantially increased in the last 39 years.
Nanoscale transfer of angular momentum mediated by the Casimir torque
Authors: Sanders Stephen , Kort-Kamp Wilton J. M. , Dalvit Diego A. R. , Manjavacas Alejandro 
Published: June 2019

AbstractCasimir interactions play an important role in the dynamics of nanoscale objects. Here, we investigate the noncontact transfer of angular momentum at the nanoscale through the analysis of the Casimir torque acting on a chain of rotating nanoparticles. We show that this interaction, which arises from the vacuum and thermal fluctuations of the electromagnetic field, enables an efficient transfer of angular momentum between the elements of the chain. Working within the framework of fluctuational electrodynamics, we derive analytical expressions for the Casimir torque acting on each nanoparticle in the chain, which we use to study the synchronization of chains with different geometries and to predict unexpected dynamics, including a “rattleback”-like behavior. Our results provide insights into the Casimir torque and how it can be exploited to achieve efficient noncontact transfer of angular momentum at the nanoscale, and therefore have important implications for the control and manipulation of nanomechanical devices.
Heterozygous RHO p.R135W missense mutation in a large Han-Chinese family with retinitis pigmentosa and different refractive errors
Authors: Wu Yuan , Guo Yi , Yi Junhui , Xu Hongbo , Yuan Lamei , Yang Zhijian , Deng Hao 
Published: June 2019

Abstract
Retinitis pigmentosa (RP), the most common type of inherited retinal degeneration causing blindness, initially manifests as severely impaired rod function followed by deteriorating cone function. Mutations in the rhodopsin gene (RHO) are the most common cause of autosomal dominant RP (adRP). The present study aims to identify the disease-causing mutation in a numerous, four-generation Han-Chinese family with adRP detected by whole exome sequencing and Sanger sequencing. Afflicted family members present classic adRP along with heterogeneous clinical phenotypes including differing refractive errors, cataracts, astigmatism and epiretinal membranes. A missense mutation, c.403C&gt;T (p.R135W), in the RHO gene was identified in nine subjects and it co-segregated with family members. The mutation is predicted to be disease-causing and results in rhodopsin protein abnormalities. The present study extends the genotype–phenotype relationship between RHO gene mutations and adRP clinical findings. The results have implications for familial genetic counseling, clinical management and developing RP target gene therapy strategies.
H2S attenuates endoplasmic reticulum stress in hypoxia-induced pulmonary artery hypertension
Authors: Wu Jianjun , Pan Weili , Wang Chao , Dong Hui , Xing Lei , Hou Jingbo , Fang Shaohong , Li Hulun , Yang Fan , Yu Bo 
Published: June 2019

Abstract
Background: Previous studies have found that hydrogen sulfide (H2S) has multiple functions such as anti-inflammatory, antioxidative in addition to biological effects among the various organs. Exaggerated proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) is a key component of vascular remodeling. We hypothesized that endogenous bioactive molecular known to suppress endoplasmic reticulum (ER) stress signaling, like H2S, will inhibit the disruption of the ER-mitochondrial unit and prevent/reverse pulmonary arterial hypertension (PAH).
Methods and results: A hypoxic model was established with PASMCs to investigate the possible role of H2S in PAH. Effects of H2S on proliferation of PASMCs were evaluated by CCK-8 and EdU assay treated with or without GYY4137 (donor of H2S). H2S significantly inhibited hypoxia-induced increase in PASMCs proliferation in a dose-dependent manner. H2S by intraperitoneal injection with rats both prevented and reversed chronic hypoxia-induced pulmonary hypertension in rats, decreasing pulmonary vascular resistance, pulmonary artery remodeling and right ventricular hypertrophy, and improving functional capacity without affecting systemic hemodynamic. Exogenous H2S suppressed ER stress indexes in vivo and in vitro, decreased activating transcription factor 6 activation, and inhibited the hypoxia-induced decrease in mitochondrial calcium and mitochondrial function.
Conclusion: H2S effectively inhibits hypoxia-induced increase in cell proliferation, migration, and oxidative stress in PASMCs, and NOX-4 might be the underlying mechanism of PAH. Attenuating ER stress with exogenous H2S may be a novel therapeutic strategy in pulmonary hypertension with high translational potential.
Down-regulation of microRNA-142-3p inhibits the aggressive phenotypes of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting nuclear factor-κB signaling
Authors: Qiang Jianhong , Lv Tingting , Wu Zhenbiao , Yang Xichao 
Published: June 2019

Abstract
The present study aimed to investigate the regulatory roles of miR-142-3p on the aggressive phenotypes of rheumatoid arthritis (RA) human fibroblast-like synoviocytes (RA-HFLSs), and reveal the potential mechanisms relating with nuclear factor-κB (NF-κB) signaling. miR-142-3p expression was detected in RA synovial tissues and RA-HFLSs by quantitative real-time PCR (qRT-PCR) and Northern blot analysis. RA-HFLSs were transfected with miR-142-3p inhibitor and/or treated with 10 µg/l tumor necrosis factor α (TNF-α). The viability, colony formation, apoptosis, migration, invasion, and the levels of interleukin (IL)-6, and matrix metalloproteinase 3 (MMP-3) were detected. The mRNA expressions of B-cell lymphoma-2 (Bcl-2), Bax, Bad, IL-6, and MMP-3 were detected by qRT-PCR. Moreover, the expression of Bcl-2, IL-1 receptor-associated kinase 1 (IRAK1), Toll-like receptor 4 (TLR4), NF-κB p65, and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blot. The interaction between IRAK1 and miR-142-3p was identified by dual luciferase reporter gene assay. MiR-142-3p was up-regulated in RA synovial tissues and RA-HFLSs. TNF-α activated the aggressive phenotypes of RA-HFLSs, including enhanced proliferation, migration, invasion, and inflammation, and inhibited apoptosis. miR-142-3p inhibitor significantly decreased the cell viability, the number of cell clones, the migration rate, the number of invasive cells, the contents and expression of IL-6 and MMP-3, and increased the apoptosis rate and the expressions of Bax and Bad, and decreased Bcl-2 expression of TNF-α-treated RA-HFLSs. MiR-142-3p inhibitor significantly reversed TNF-α-induced up-regulation of IRAK1, TLR4, and p-NF-κB p65 in TNF-α-treated RA-HFLSs. Besides, IRAK1 was a target of miR-142-3p. The down-regulation of miR-142-3p inhibited the aggressive phenotypes of RA-HFLSs through inhibiting NF-κB signaling.
MicroRNA-302d promotes the proliferation of human pluripotent stem cell-derived cardiomyocytes by inhibiting LATS2 in the Hippo pathway
Authors: Xu Fei , Yang Jingcheng , Shang Jun , Lan Feng , Li Miaomiao , Shi Leming , Shen Li , Wang Yongming , Ge Junbo 
Published: June 2019

Abstract
Recent evidence has shown that cardiomyocytes (CMs) can proliferate at a low level after myocardial infarction (MI), but it is insufficient to reestablish heart function. Several microRNAs (miRNAs) have been proven to sufficiently induce rodent CM proliferation. However, whether miRNAs identified in rodents can promote human CM proliferation is unknown due to the poorly conserved functions of miRNAs among species. In the present study, we demonstrate that i) expression of microRNA-302d (miR-302d) decreased significantly during CM differentiation from human pluripotent stem cells (hPSCs) from day 4 to day 18; ii) miR-302d efficiently promoted proliferation of hPSC-derived CMs; iii) miR-302d promoted CM proliferation by targeting LATS2 in the Hippo pathway; and iv) RNA-sequencing analysis revealed that overexpression of miR-302d induced changes in gene expression, which mainly converged on the cell cycle. Our study provides further evidence for the therapeutic potential of miR-302d.
Study of CS, SiO, and SiS abundances in carbon star envelopes: assessing their role as gas-phase precursors of dust
Authors: Massalkhi S. , Agúndez M. , Cernicharo J. 
Published: June 2019

Aims. We aim to determine the abundances of CS, SiO, and SiS in a large sample of carbon star envelopes covering a wide range of mass loss rates to investigate the potential role that these molecules could play in the formation of dust in the surroundings of the central AGB star.
Methods. We surveyed a sample of 25 carbon-rich AGB stars in the λ 2 mm band, more concretely in the J = 3−2 line of CS and SiO, and in the J = 7−6 and J = 8−7 lines of SiS, using the IRAM 30 m telescope. We performed excitation and radiative transfer calculations based on the large velocity gradient (LVG) method to model the observed lines of the molecules and to derive their fractional abundances in the observed envelopes. We also assessed the effect of infrared pumping in the excitation of the molecules.
Results. We detected CS in all 25 targeted envelopes, SiO in 24 of them, and SiS in 17 sources. Remarkably, SiS is not detected in any envelope with a mass loss rate below 10−6 M⊙ yr−1 while it is detected in all envelopes with mass loss rates above that threshold. We found that CS and SiS have similar abundances in carbon star envelopes, while SiO is present with a lower abundance. We also found a strong correlation in which the denser the envelope, the less abundant are CS and SiO. The trend is however only tentatively seen for SiS in the range of high mass loss rates. Furthermore, we found a relation in which the integrated flux of the MgS dust feature at 30 μm increases as the fractional abundance of CS decreases.
Conclusions. The decline in the fractional abundance of CS with increasing density could be due to gas-phase chemistry in the inner envelope or to adsorption onto dust grains. The latter possibility is favored by a correlation between the CS fractional abundance and the 30 μm feature, which suggests that CS is efficiently incorporated onto MgS dust around C-rich AGB stars. In the case of SiO, the observed abundance depletion with increasing density is most likely caused by an efficient incorporation onto dust grains. We conclude that CS, SiO (very likely), and SiS (tentatively) are good candidates to act as gas-phase precursors of dust in C-rich AGB envelopes.
Using the infrared iron lines to probe solar subsurface convection
Authors: Milić I. , Smitha H. N. , Lagg A. 
Published: June 2019

Context. Studying the properties of solar convection using high-resolution spectropolarimetry began in the early 1990s with the focus on observations in the visible wavelength regions. Its extension to the infrared (IR) remains largely unexplored.
Aims. The IR iron lines around 15 600 Å, most commonly known for their high magnetic sensitivity, also have a non-zero response to line-of-sight (LOS) velocity below log(τ) = 0.0. In this paper we explore the possibility of using these lines to measure subsurface convective velocities.
Methods. By assuming a snapshot of a three-dimensional magnetohydrodynamic simulation to represent the quiet Sun, we investigate how well the iron IR lines can reproduce the LOS velocity in the cube and to what depth. We use the recently developed spectropolarimetric inversion code SNAPI and discuss the optimal node placements for the retrieval of reliable results from these spectral lines.
Results. We find that the IR iron lines can measure the convective velocities down to log(τ) = 0.5, below the photosphere, not only at the original resolution of the cube, but also when degraded with a reasonable spectral and spatial PSF and stray light. Instead, the commonly used Fe I 6300 Å line pair performs significantly worse.
Conclusions. Our investigation reveals that the IR iron lines can probe the subsurface convection in the solar photosphere. This paper is a first step towards exploiting this diagnostic potential.