bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct RNA sequencing on nanopore arrays redefines the transcriptional complexity of a viral pathogen
Authors: Depledge Daniel P. , Srinivas Kalanghad Puthankalam , Sadaoka Tomohiko , Bready Devin , Mori Yasuko , Placantonakis Dimitris G. , Mohr Ian , Wilson Angus C. 
Published: February 2019

AbstractCharacterizing complex viral transcriptomes by conventional RNA sequencing approaches is complicated by high gene density, overlapping reading frames, and complex splicing patterns. Direct RNA sequencing (direct RNA-seq) using nanopore arrays offers an exciting alternative whereby individual polyadenylated RNAs are sequenced directly, without the recoding and amplification biases inherent to other sequencing methodologies. Here we use direct RNA-seq to profile the herpes simplex virus type 1 (HSV-1) transcriptome during productive infection of primary cells. We show how direct RNA-seq data can be used to define transcription initiation and RNA cleavage sites associated with all polyadenylated viral RNAs and demonstrate that low level read-through transcription produces a novel class of chimeric HSV-1 transcripts, including a functional mRNA encoding a fusion of the viral E3 ubiquitin ligase ICP0 and viral membrane glycoprotein L. Thus, direct RNA-seq offers a powerful method to characterize the changing transcriptional landscape of viruses with complex genomes.
Nanometric axial resolution of fibronectin assembly units achieved with an efficient reconstruction approach for multi-angle-TIRF microscopy
Authors: Soubies Emmanuel , Radwanska Agata , Grall Dominique , Blanc-Féraud Laure , Van Obberghen-Schilling Ellen , Schaub Sébastien 
Published: February 2019

AbstractHigh resolution imaging of molecules at the cell-substrate interface is required for understanding key biological processes. Here we propose a complete pipeline for multi-angle total internal reflection fluorescence microscopy (MA-TIRF) going from instrument design and calibration procedures to numerical reconstruction. Our custom setup is endowed with a homogeneous field illumination and precise excitation beam angle. Given a set of MA-TIRF acquisitions, we deploy an efficient joint deconvolution/reconstruction algorithm based on a variational formulation of the inverse problem. This algorithm offers the possibility of using various regularizations and can run on graphics processing unit (GPU) for rapid reconstruction. Moreover, it can be easily used with other MA-TIRF devices and we provide it as an open-source software. This ensemble has enabled us to visualize and measure with unprecedented nanometric resolution, the depth of molecular components of the fibronectin assembly machinery at the basal surface of endothelial cells.
Antibody-mediated biorecognition of myelin oligodendrocyte glycoprotein: computational evidence of demyelination-related epitopes
Authors: Ierich Jéssica Cristiane Magalhães , Brum Doralina Guimarães , Moraes Ariana de Souza , Higa Akemi Martins , Garcia Pâmela Soto , Miyazaki Celina Massumi , Ferreira Marystela , Peroni Luís Antonio , Oliveira Guedmiller Souza de , Franca Eduardo de Faria , Freitas Luiz Carlos Gomide , Leite Fabio Lima 
Published: February 2019

AbstractAntigen-antibody interaction is crucial in autoimmune disease pathogenesis, as multiple sclerosis and neuromyelitis optica. Given that, autoantibodies are essential biomolecules, of which the myelin oligodendrocyte glycoprotein (MOG) can figure as a target. Here we combined Molecular Dynamics (MD), Steered Molecular Dynamics (SMD), and Atomic Force Microscope (AFM) to detail MOG recognition by its specific antibody. The complex model consisted of the MOG external domain interacting with an experimental anti-MOG antibody from the Protein Data Bank (1PKQ). Computational data demonstrated thirteen MOG residues with a robust contribution to the antigen-antibody interaction. Comprising five of the thirteen anchor residues (ASP102, HIS103, SER104, TYR105, and GLN106), the well-known MOG92–106peptide in complex with the anti-MOG was analysed by AFM and SMD. These analyses evidenced similar force values of 780 pN and 765 pN for computational and experimental MOG92–106and anti-MOG detachment, respectively. MOG92–106was responsible for 75% of the total force measured between MOG external domain and anti-MOG, holding the interaction with the antibody. The antigen-antibody binding was confirmed by Surface Plasmon Resonance (SPR) measurements. Combined approaches presented here can conveniently be adjusted to detail novel molecules in diseases research. This can optimize pre-clinical steps, guiding experiments, reducing costs, and animal model usage.
Development and validation of whole genome-wide and genic microsatellite markers in oil palm (Elaeis guineensis Jacq.): First microsatellite database (OpSatdb)
Authors: B. Kalyana Babu , K. L. Mary Rani , Sahu Sarika , Mathur R. K. , P. Naveen Kumar , G. Ravichandran , P. Anitha , H. P. Bhagya 
Published: February 2019

AbstractThe availability of large expressed sequence tag (EST) and whole genome databases of oil palm enabled the development of a data base of microsatellite markers. For this purpose, an EST database consisting of 40,979 EST sequences spanning 27 Mb and a chromosome-wise whole genome databases were downloaded. A total of 3,950 primer pairs were identified and developed from EST sequences. The tri and tetra nucleotide repeat motifs were most prevalent (each 24.75%) followed by di-nucleotide repeat motifs. Whole genome-wide analysis found a total of 245,654 SSR repeats across the 16 chromosomes of oil palm, of which 38,717 were compound microsatellite repeats. A web application, OpSatdb, the first microsatellite database of oil palm, was developed using the PHP and MySQL database (https://ssr.icar.gov.in/index.php). It is a simple and systematic web-based search engine for searching SSRs based on repeat motif type, repeat type, and primer details. High synteny was observed between oil palm and rice genomes. The mapping of ESTs having SSRs by Blast2GO resulted in the identification of 19.2% sequences with gene ontology (GO) annotations. Randomly, a set of ten genic SSRs and five genomic SSRs were used for validation and genetic diversity on 100 genotypes belonging to the world oil palm genetic resources. The grouping pattern was observed to be broadly in accordance with the geographical origin of the genotypes. The identified genic and genome-wide SSRs can be effectively useful for various genomic applications of oil palm, such as genetic diversity, linkage map construction, mapping of QTLs, marker-assisted selection, and comparative population studies.
How context influences the interpretation of facial expressions: a source localization high-density EEG study on the “Kuleshov effect”
Authors: Calbi Marta , Siri Francesca , Heimann Katrin , Barratt Daniel , Gallese Vittorio , Kolesnikov Anna , Umiltà Maria Alessandra 
Published: February 2019

AbstractFew studies have explored the specificities of contextual modulations of the processing of facial expressions at a neuronal level. This study fills this gap by employing an original paradigm, based on a version of the filmic “Kuleshov effect”. High-density EEG was recorded while participants watched film sequences consisting of three shots: the close-up of a target person’s neutral face (Face_1), the scene that the target person was looking at (happy, fearful, or neutral), and another close-up of the same target person’s neutral face (Face_2). The participants’ task was to rate both valence and arousal, and subsequently to categorize the target person’s emotional state. The results indicate that despite a significant behavioural ‘context’ effect, the electrophysiological indexes still indicate that the face is evaluated as neutral. Specifically, Face_2 elicited a high amplitude N170 when preceded by neutral contexts, and a high amplitude Late Positive Potential (LPP) when preceded by emotional contexts, thus showing sensitivity to the evaluative congruence (N170) and incongruence (LPP) between context and Face_2. The LPP activity was mainly underpinned by brain regions involved in facial expressions and emotion recognition processing. Our results shed new light on temporal and neural correlates of context-sensitivity in the interpretation of facial expressions.
Triggering The Birth of New Cycle’s Sunspots by Solar Tsunami
Authors: Dikpati Mausumi , McIntosh Scott W. , Chatterjee Subhamoy , Banerjee Dipankar , Yellin-Bergovoy Ron , Srivastava Abhishek 
Published: February 2019

AbstractWhen will a new cycle’s sunspots appear? We demonstrate a novel physical mechanism, namely, that a “solar tsunami” occurring in the Sun’s interior shear-fluid layer can trigger new cycle’s magnetic flux emergence at high latitudes, a few weeks after the cessation of old cycle’s flux emergence near the equator. This tsunami is excited at the equator when magnetic dams, created by the oppositely-directed old cycle’s toroidal field in North and South hemispheres, break due to mutual annihilation of toroidal flux there. The fluid supported by these dams rushes to the equator; the surplus of fluid cannot be contained there, so it reflects back towards high latitudes, causing a tsunami. This tsunami propagates poleward at a speed of ~300 m/s until it encounters the new cycle’s spot-producing toroidal fields in mid-latitudes, where it perturbs the fields, triggering their surface-eruption in the form of new cycle spots. A new sunspot cycle is preceded for several years by other forms of high-latitude magnetic activity, such as coronal bright points and ephemeral regions, until the tsunami causes the birth of new cycle’s spots. The next tsunami is due by 2020, portending the start of intense ‘space weather’ that can adversely impact the Earth.
Expression, activity and localization of lysosomal sulfatases in Chronic Obstructive Pulmonary Disease
Authors: Weidner Julie , Jogdand Prajakta , Jarenbäck Linnea , Åberg Ida , Helihel Dalja , Ankerst Jaro , Westergren-Thorsson Gunilla , Bjermer Leif , Erjefält Jonas S. , Tufvesson Ellen 
Published: February 2019

AbstractChronic obstructive pulmonary disease (COPD) is a leading cause of death world-wide. Recently, we showed that COPD is associated with gene polymorphisms in SUMF1, a master regulator of sulfatases. Sulfatases are involved in extracellular matrix remodeling and activated by SUMF1, but their role in the lung is poorly described. We aimed to examine how sulfatases are affected in the airways of patients with COPD compared to ever smokers and never smokers. We observed that mRNA expression of the sulfatases GALNS, GNS and IDS was increased, while protein expression of many sulfatases was decreased in COPD fibroblasts. Several sulfatases, including GALNS, IDS, and SGSH, showed increased activity in COPD fibroblasts. Examination of different sulfatases by immunofluorescence showed that IDS, ARSB, GNS and SGSH in fibroblasts were localized to sites other than their reported destination. Using a master panel from different organs, RNA expression of all sulfatases could be observed in lung tissue. Additionally, immunohistochemistry on lung biopsies indicated differing expression of sulfatases in COPD patients. In conclusion, mRNA, protein expression, sulfatase activity levels, and localization of sulfatases are altered in lung fibroblasts and lung tissue from COPD patients and may be mechanistically important in COPD pathogenesis. This could contribute to the understanding of the disease mechanism in COPD and in the long run, to lead to more individualized therapies.
Corpora amylacea in human hippocampal brain tissue are intracellular bodies that exhibit a homogeneous distribution of neo-epitopes
Authors: Augé Elisabet , Bechmann Ingo , Llor Núria , Vilaplana Jordi , Krueger Martin , Pelegrí Carme 
Published: February 2019

AbstractCorpora amylacea are spherical bodies of unknown origin and function, which accumulate in the human brain during the aging process and neurodegenerative disorders. In recent work, we reported that they contain some neo-epitopes that are recognized by natural IgMs, revealing a possible link between them and the natural immune system. Here, we performed an ultrastructural study complemented with confocal microscopy in order to shed light on the formation of corpora amylacea and to precisely localize the neo-epitopes. We show that immature corpora amylacea are intracellular astrocytic structures formed by profuse cellular debris and membranous blebs entrapped in a scattered mass of randomly oriented short linear fibers. In mature corpora amylacea, the structure becomes compacted and fibrillary material constitutes the principal component. We also determined that the neo-epitopes were uniformly localized throughout the whole structure. All these observations reinforce the idea that corpora amylacea of human brain are equivalent to another type of polyglucosan bodies named PAS granules, present in mouse brain and originated from degenerative processes. All those findings support the hypothesis that corpora amylacea are involved in the entrapment of damaged materials and non-degradable products and have a role in protective or cleaning mechanisms.
Integrative taxonomy of a new Redudasys species (Gastrotricha: Macrodasyida) sheds light on the invasion of fresh water habitats by macrodasyids
Authors: Garraffoni André R. S. , Araújo Thiago Q. , Lourenço Anete P. , Guidi Loretta , Balsamo Maria 
Published: February 2019

AbstractThe order Macrodasyida (Gastrotricha) includes over 350 marine species, and only 3 freshwater species (Marinellina flagellata, Redudasys fornerise, R. neotemperatus). Herein we describe a new freshwater species of Macrodasyida, Redudasys brasiliensis sp. nov., from Brazil through an integrative taxonomic approach. The external morphology and internal anatomy were investigated using differential interference contrast microscopy, confocal microscopy, scanning and transmission electron microscopy. The systematization of the new taxon was inferred by nuclear (18S and 28S) and mitochondrial (COI) genes, and its intra-order relationships were assessed using data from most of available macrodasyids. Phylogenetic analyses yielded congruent trees, in which the new taxon is nested within the family Redudasyidae, but it was genetically distinct from the other species of the genus Redudasys. The new species shares the gross morphology and reproductive traits with other Redudasyidae and the presence of only 1 anterior adhesive tube per side with Redudasys neotemperatus, but it has a specific pattern of ventral ciliation and muscle organization. Results support the hypothesis that dispersion into fresh water habitats by Macrodasyida and Chaetonotida taxa occurred independently and that within Macrodasyida a single lineage invaded the freshwater environment only once. Furthermore, the Neotropical region seems to be peculiar for the evolution of the freshwater macrodasyid clade.
Thermodynamic Signatures of Weyl Fermions in NbP
Authors: Modic K. A. , Meng Tobias , Ronning Filip , Bauer Eric D. , Moll Philip J. W. , Ramshaw B. J. 
Published: February 2019

AbstractWe present a high magnetic field study of NbP—a member of the monopnictide Weyl semimetal (WSM) family. While the monoarsenides (NbAs and TaAs) have topologically distinct left and right-handed Weyl fermi surfaces, NbP is argued to be “topologically trivial” due to the fact that all pairs of Weyl nodes are encompassed by a single Fermi surface. We use torque magnetometry to measure the magnetic response of NbP up to 60 tesla and uncover a Berry paramagnetic response, characteristic of the topological Weyl nodes, across the entire field range. At the quantum limit B* (≈32 T), τ/B experiences a change in slope when the chemical potential enters the last Landau level. Our calculations confirm that this magnetic response arises from band topology of the Weyl pocket, even though the Fermi surface encompasses both Weyl nodes at zero magnetic field. We also find that the magnetic field pulls the chemical potential to the chiral n = 0 Landau level in the quantum limit, providing a disorder-free way of accessing chiral Weyl fermions in systems that are “not quite” WSMs in zero magnetic field.
Quantifying dynamic mechanisms of auto-regulation in Escherichia coli with synthetic promoter in response to varying external phosphate levels
Authors: Uluşeker Cansu , Torres-Bacete Jesús , García José L. , Hanczyc Martin M. , Nogales Juan , Kahramanoğulları Ozan 
Published: February 2019

AbstractEscherichia coli have developed one of the most efficient regulatory response mechanisms to phosphate starvation. The machinery involves a cascade with a two-component system (TCS) that relays the external signal to the genetic circuit, resulting in a feedback response. Achieving a quantitative understanding of this system has implications in synthetic biology and biotechnology, for example, in applications for wastewater treatment. To this aim, we present a computational model and experimental results with a detailed description of the TCS, consisting of PhoR and PhoB, together with the mechanisms of gene expression. The model is parameterised within the feasible range, and fitted to the dynamic response of our experimental data on PhoB as well as PhoA, the product of this network that is used in alkaline phosphatase production. Deterministic and stochastic simulations with our model predict the regulation dynamics in higher external phosphate concentrations while reproducing the experimental observations. In a cycle of simulations and experimental verification, our model predicts and explores phenotypes with various synthetic promoter designs that can optimise the inorganic phosphate intake in E. coli. Sensitivity analysis demonstrates that the Pho-controlled genes have a significant influence over the phosphate response. Together with experimental findings, our model should thus provide insights for the investigations on engineering new sensors and regulators for living technologies.
Network controllability analysis of intracellular signalling reveals viruses are actively controlling molecular systems
Authors: Ravindran Vandana , Nacher Jose C. , Akutsu Tatsuya , Ishitsuka Masayuki , Osadcenco Adrian , Sunitha V. , Bagler Ganesh , Schwartz Jean-Marc , Robertson David L. 
Published: February 2019

AbstractIn recent years control theory has been applied to biological systems with the aim of identifying the minimum set of molecular interactions that can drive the network to a required state. However, in an intra-cellular network it is unclear how control can be achieved in practice. To address this limitation we use viral infection, specifically human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV), as a paradigm to model control of an infected cell. Using a large human signalling network comprised of over 6000 human proteins and more than 34000 directed interactions, we compared two states: normal/uninfected and infected. Our network controllability analysis demonstrates how a virus efficiently brings the dynamically organised host system into its control by mostly targeting existing critical control nodes, requiring fewer nodes than in the uninfected network. The lower number of control nodes is presumably to optimise exploitation of specific sub-systems needed for virus replication and/or involved in the host response to infection. Viral infection of the human system also permits discrimination between available network-control models, which demonstrates that the minimum dominating set (MDS) method better accounts for how the biological information and signals are organised during infection by identifying most viral proteins as critical driver nodes compared to the maximum matching (MM) method. Furthermore, the host driver nodes identified by MDS are distributed throughout the pathways enabling effective control of the cell via the high ‘control centrality’ of the viral and targeted host nodes. Our results demonstrate that control theory gives a more complete and dynamic understanding of virus exploitation of the host system when compared with previous analyses limited to static single-state networks.
In vivo characterization of doxycycline-mediated protection of aortic function and structure in a mouse model of Marfan syndrome-associated aortic aneurysm
Authors: Cui Jason Z. , Lee Ling , Sheng Xiaoye , Chu Fanny , Gibson Christine P. , Aydinian Taline , Walker David C. , Sandor George G. S. , Bernatchez Pascal , Tibbits Glen F. , van Breemen Cornelis , Esfandiarei Mitra 
Published: February 2019

AbstractAortic aneurysm is the most life-threatening complication in Marfan syndrome (MFS) patients. Doxycycline, a nonselective matrix metalloproteinases inhibitor, was reported to improve the contractile function and elastic fiber structure and organization in a Marfan mouse aorta usingex vivosmall chamber myography. In this study, we assessed the hypothesis that a long-term treatment with doxycycline would reduce aortic root growth, improve aortic wall elasticity as measured by pulse wave velocity, and improve the ultrastructure of elastic fiber in the mouse model of MFS. In our study, longitudinal measurements of aortic root diameters using high-resolution ultrasound imaging display significantly decreased aortic root diameters and lower pulse wave velocity in doxycycline-treated Marfan mice starting at 6 months as compared to their non-treated MFS counterparts. In addition, at the ultrastructural level, our data show that long-term doxycycline treatment corrects the irregularities of elastic fibers within the aortic wall of Marfan mice to the levels similar to those observed in control subjects. Our findings underscore the key role of matrix metalloproteinases during the progression of aortic aneurysm, and provide new insights into the potential therapeutic value of doxycycline in blocking MFS-associated aortic aneurysm.
Selective Inactivation of Intracellular BiP/GRP78 Attenuates Endothelial Inflammation and Permeability in Acute Lung Injury
Authors: Leonard Antony , Grose Valerie , Paton Adrienne W. , Paton James C. , Yule David I. , Rahman Arshad , Fazal Fabeha 
Published: February 2019

AbstractThe role of Endoplasmic Reticulum Chaperone and Signaling Regulator BiP/GRP78 in acute inflammatory injury, particularly in the context of lung endothelium, is poorly defined. In his study, we monitored the effect of SubAB, a holoenzyme that cleaves and specifically inactivates BiP/GRP78 and its inactive mutant SubAA272B on lung inflammatory injury in an aerosolized LPS inhalation mouse model of acute lung injury (ALI). Analysis of lung homogenates and bronchoalveolar lavage (BAL) fluid showed that LPS-induced lung inflammation and injury were significantly inhibited in SubAB- but not in SubAA272B-treated mice. SubAB-treated mice were also protected from LPS-induced decrease in lung compliance. Gene transfer of dominant negative mutant of BiP in the lung endothelium protected against LPS-induced lung inflammatory responses. Consistent with this, stimulation of endothelial cells (EC) with thrombin caused an increase in BiP/GRP78 levels and inhibition of ER stress with 4-phenylbutyric acid (4-PBA) prevented this response as well as increase in VCAM-1, ICAM-1, IL-6, and IL-8 levels. Importantly, thrombin-induced Ca2+ signaling and EC permeability were also prevented upon BiP/GRP78 inactivation. The above EC responses are mediated by intracellular BiP/GRP78 and not by cell surface BiP/GRP78. Together, these data identify intracellular BiP/GRP78 as a novel regulator of endothelial dysfunction associated with ALI.