bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weaker neural suppression in autism
Authors: Schallmo Michael-Paul , Kolodny Tamar , Kale Alexander M. , Millin Rachel , Flevaris Anastasia V. , Edden Richard A. E. , Gerdts Jennifer , Bernier Raphael A. , Murray Scott O. 
Published: May 2020

AbstractAbnormal sensory processing has been observed in autism, including superior visual motion discrimination, but the neural basis for these sensory changes remains unknown. Leveraging well-characterized suppressive neural circuits in the visual system, we used behavioral and fMRI tasks to demonstrate a significant reduction in neural suppression in young adults with autism spectrum disorder (ASD) compared to neurotypical controls. MR spectroscopy measurements revealed no group differences in neurotransmitter signals. We show how a computational model that incorporates divisive normalization, as well as narrower top-down gain (that could result, for example, from a narrower window of attention), can explain our observations and divergent previous findings. Thus, weaker neural suppression is reflected in visual task performance and fMRI measures in ASD, and may be attributable to differences in top-down processing.
Lipid Nanoparticle Formulation Increases Efficiency of DNA-Vectored Vaccines/Immunoprophylaxis in Animals Including Transchromosomic Bovines
Authors: Mucker Eric M. , Karmali Priya P. , Vega Jerel , Kwilas Steven A. , Wu Hua , Joselyn Matthew , Ballantyne John , Sampey Darryl , Mukthavaram Rajesh , Sullivan Eddie , Chivukula Pad , Hooper Jay W. 
Published: May 2020

AbstractThe use of nucleic acid as a drug substance for vaccines and other gene-based medicines continues to evolve. Here, we have used a technology originally developed for mRNA in vivo delivery to enhance the immunogenicity of DNA vaccines. We demonstrate that neutralizing antibodies produced in rabbits and nonhuman primates injected with lipid nanoparticle (LNP)-formulated Andes virus or Zika virus DNA vaccines are elevated over unformulated vaccine. Using a plasmid encoding an anti-poxvirus monoclonal antibody (as a reporter of protein expression), we showed that improved immunogenicity is likely due to increased in vivo DNA delivery, resulting in more target protein. Specifically, after four days, up to 30 ng/mL of functional monoclonal antibody were detected in the serum of rabbits injected with the LNP-formulated DNA. We pragmatically applied the technology to the production of human neutralizing antibodies in a transchromosomic (Tc) bovine for use as a passive immunoprophylactic. Production of neutralizing antibody was increased by >10-fold while utilizing 10 times less DNA in the Tc bovine. This work provides a proof-of-concept that LNP formulation of DNA vaccines can be used to produce more potent active vaccines, passive countermeasures (e.g., Tc bovine), and as a means to produce more potent DNA-launched immunotherapies.
Colorectal cancer is associated with increased circulating lipopolysaccharide, inflammation and hypercoagulability
Authors: de Waal Greta M. , de Villiers Willem J. S. , Forgan Timothy , Roberts Timothy , Pretorius Etheresia 
Published: May 2020

AbstractGut dysbiosis contributes to the development of a dysfunctional gut barrier, facilitating the translocation of bacteria and inflammagens, and is implicated in colorectal cancer (CRC) pathogenesis. Such ‘leaky gut’ conditions result in systemic inflammation, of which a hallmark is increased hypercoagulability. Fluorescence antibody confocal microscopy was used to determine circulating levels of lipopolysaccharide (LPS) in control and CRC populations. Here we showed that circulating levels of LPS are significantly elevated in the CRC population. We also showed that markers of inflammation and hypercoagulability are increased in this population. Furthermore, anomalous blood clotting and structural changes in blood components are presented. Importantly, the association between LPS levels, inflammation, and hematological dysfunction was analysed. Statistical regression models were applied to identify markers with strong association with CRC, and to investigate the correlation between markers. A core aim is enhanced biomarker discovery for CRC. We conclude that circulating LPS can promote systemic inflammation and contribute to the development of a pathological coagulation system, with resulting chronic inflammation and an activated coagulation system implicated in tumorigenesis. Blood-based screening tools are an emerging research area of interest for CRC screening. We propose the use of additional (novel) biomarkers to effectively screen for CRC.
Soluble HLA-G expression levels and HLA-G/irinotecan association in metastatic colorectal cancer treated with irinotecan-based strategy
Authors: Scarabel Lucia , Garziera Marica , Fortuna Sara , Asaro Fioretta , Toffoli Giuseppe , Geremia Silvano 
Published: May 2020

AbstractWe here explore the soluble Human Leukocyte Antigen-G (sHLA-G) expression level as clinical biomarker in metastatic colorectal cancer (mCRC). To this aim the sHLA-G protein was measured in plasma samples of 40 patients with mCRC treated with the FOLFIRI (irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and leucovorin (LV)) regimen. The results suggest a link between HLA-G levels and irinotecan (CPT-11) pharmacokinetic, leading to hypothesize a molecular interaction between sHLA-G and CPT-11. This interaction was confirmed experimentally by fluorescence spectroscopy. HLA-G is known to exist in a number of polymorphs that affect both the protein expression levels and its peptide-binding cleft. The interaction between HLA-G polymorphs and CPT-11 was explored by means of computational modelling, confirming the hypothesis that CPT-11 could actually target the peptide binding cleft of the most common HLA-G polymorphs.
BAG3 Pro209 mutants associated with myopathy and neuropathy relocate chaperones of the CASA-complex to aggresomes
Authors: Adriaenssens Elias , Tedesco Barbara , Mediani Laura , Asselbergh Bob , Crippa Valeria , Antoniani Francesco , Carra Serena , Poletti Angelo , Timmerman Vincent 
Published: May 2020

AbstractThree missense mutations targeting the same proline 209 (Pro209) codon in the co-chaperone Bcl2-associated athanogene 3 (BAG3) have been reported to cause distal myopathy, dilated cardiomyopathy or Charcot-Marie-Tooth type 2 neuropathy. Yet, it is unclear whether distinct molecular mechanisms underlie the variable clinical spectrum of the rare patients carrying these three heterozygous Pro209 mutations in BAG3. Here, we studied all three variants and compared them to the BAG3_Glu455Lys mutant, which causes dilated cardiomyopathy. We found that all BAG3_Pro209 mutants have acquired a toxic gain-of-function, which causes these variants to accumulate in the form of insoluble HDAC6- and vimentin-positive aggresomes. The aggresomes formed by mutant BAG3 led to a relocation of other chaperones such as HSPB8 and Hsp70, which, together with BAG3, promote the so-called chaperone-assisted selective autophagy (CASA). As a consequence of their increased aggregation-proneness, mutant BAG3 trapped ubiquitinylated client proteins at the aggresome, preventing their efficient clearance. Combined, these data show that all BAG3_Pro209 mutants, irrespective of their different clinical phenotypes, are characterized by a gain-of-function that contributes to the gradual loss of protein homeostasis.
Cold climate adaptation is a plausible cause for evolution of multicellular sporulation in Dictyostelia
Authors: Lawal Hajara M. , Schilde Christina , Kin Koryu , Brown Matthew W. , James John , Prescott Alan R. , Schaap Pauline 
Published: May 2020

AbstractUnicellular protozoa that encyst individually upon starvation evolved at least eight times into organisms that instead form multicellular fruiting bodies with spores. The Dictyostelia are the largest and most complex group of such organisms. They can be subdivided into 4 major groups, with many species in groups 1–3 having additionally retained encystment. To understand fitness differences between spores and cysts, we measured long-term survival of spores and cysts under climate-mimicking conditions, investigated spore and cyst ultrastructure, and related fitness characteristics to species ecology. We found that spores and cysts survived 22 °C equally well, but that spores survived wet and dry frost better than cysts, with group 4 spores being most resilient. Spore walls consist of three layers and those of cysts of maximally two, while spores were also more compacted than cysts, with group 4 spores being the most compacted. Group 4 species were frequently isolated from arctic and alpine zones, which was rarely the case for group 1–3 species. We inferred a fossil-calibrated phylogeny of Dictyostelia, which showed that its two major branches diverged 0.52 billion years ago, following several global glaciations. Our results suggest that Dictyostelium multicellular sporulation was a likely adaptation to a cold climate.
Exercise efficiency impairment in metabolic myopathies
Authors: Noury Jean-Baptiste , Zagnoli Fabien , Petit François , Marcorelles Pascale , Rannou Fabrice 
Published: May 2020

AbstractMetabolic myopathies are muscle disorders caused by a biochemical defect of the skeletal muscle energy system resulting in exercise intolerance. The primary aim of this research was to evaluate the oxygen cost (∆V’O2/∆Work-Rate) during incremental exercise in patients with metabolic myopathies as compared with patients with non-metabolic myalgia and healthy subjects. The study groups consisted of eight patients with muscle glycogenoses (one Tarui and seven McArdle diseases), seven patients with a complete and twenty-two patients with a partial myoadenylate deaminase (MAD) deficiency in muscle biopsy, five patients with a respiratory chain deficiency, seventy-three patients with exercise intolerance and normal muscle biopsy (non-metabolic myalgia), and twenty-eight healthy controls. The subjects underwent a cardiopulmonary exercise test (CPX Medgraphics) performed on a bicycle ergometer. Pulmonary V’O2 was measured breath-by-breath throughout the incremental test. The ∆V’O2/∆Work-Rate slope for exercise was determined by linear regression analysis. Lower oxygen consumption (peak percent of predicted, mean ± SD; p < 0.04, one-way ANOVA) was seen in patients with glycogenoses (62.8 ± 10.2%) and respiratory chain defects (70.8 ± 23.3%) compared to patients with non-metabolic myalgia (100.0 ± 15.9%) and control subjects (106.4 ± 23.5%). ∆V’O2/∆Work-Rate slope (mLO2.min−1.W−1) was increased in patients with MAD absent (12.6 ± 1.5), MAD decreased (11.3 ± 1.1), glycogenoses (14.0 ± 2.5), respiratory chain defects (13.1 ± 1.2), and patients with non-metabolic myalgia (11.3 ± 1.3) compared with control subjects (10.2 ± 0.7; p < 0.001, one-way ANOVA). In conclusion, patients with metabolic myopathies display an increased oxygen cost during exercise and therefore can perform less work for a given VO2 consumption during daily life-submaximal exercises.
A mouse model that is immunologically tolerant to reporter and modifier proteins
Authors: Bresser Kaspar , Dijkgraaf Feline E. , Pritchard Colin E. J. , Huijbers Ivo J. , Song Ji-Ying , Rohr Jan C. , Scheeren Ferenc A. , Schumacher Ton N. 
Published: May 2020

AbstractReporter proteins have become an indispensable tool in biomedical research. However, exogenous introduction of these reporters into mice poses a risk of rejection by the immune system. Here, we describe the generation, validation and application of a multiple reporter protein tolerant ‘Tol' mouse model that constitutively expresses an assembly of shuffled reporter proteins from a single open reading frame. We demonstrate that expression of the Tol transgene results in the deletion of CD8+ T cells specific for a model epitope, and substantially improves engraftment of reporter-gene transduced T cells. The Tol strain provides a valuable mouse model for cell transfer and viral-mediated gene transfer studies, and serves as a methodological example for the generation of poly-tolerant mouse strains.
Framework with cytoskeletal actin filaments forming insect footpad hairs inspires biomimetic adhesive device design
Authors: Kimura Ken-ichi , Minami Ryunosuke , Yamahama Yumi , Hariyama Takahiko , Hosoda Naoe 
Published: May 2020

AbstractFootpads allow insects to walk on smooth surfaces. Specifically, liquid secretions on the footpad mediate adhesiveness through Van der Waals, Coulomb, and attractive capillary forces. Although the morphology and function of the footpad are well defined, the mechanism underlying their formation remains elusive. Here, we demonstrate that footpad hair in Drosophila is formed by the elongation of the hair cells and assembly of actin filaments. Knockdown of Actin5C caused a malformation of the hair structure, resulting in reduced ability to adhere to smooth substrates. We determined that functional footpads are created when hair cells form effective frameworks with actin filament bundles, thereby shaping the hair tip and facilitating cuticular deposition. We adapted this mechanism of microstructure formation to design a new artificial adhesive device⁠—a spatula-like fiber-framed adhesive device supported by nylon fibers with a gel material at the tip. This simple self-assembly mechanism facilitates the energy-efficient production of low-cost adhesion devices.
Potential antiviral agents of Rosmarinus officinalis extract against herpes viruses 1 and 2
Authors: AL-Megrin Wafa A. , AlSadhan Norah A. , Metwally Dina M. , Al-Talhi Razan A. , El-Khadragy Manal F. , Abdel-Hafez Lina J. M. 
Published: May 2020

Abstract
Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) belong to the herpesviridae family and cause neurological disorders by infecting the nervous system. The present study aimed to investigate the effects of Rosmarinus officinalis L. (rosemary) extract against HSV-1 and HSV-2 in vitro. The antioxidant activity of this extract was investigated by superoxide anion and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical assays. Rosemary extract was evaluated by an HSV-1 antiviral assay, in which viral replication in Vero cells was determined and quantified using a cytopathic effect assay. The present study showed that rosemary extract at 30 µg/ml caused 55% inhibition of HSV-1 plaques, whereas 40 µg/ml rosemary extract caused 65% inhibition of HSV-2 plaques. The extracts completely inhibited HSV-1 and HSV-2 plaque formation at 50 µg/ml. Scavenging activity of the superoxide anion radical was observed at 65.74 mg/ml, whereas 50% scavenging activity of the DPPH radical was observed at 67.34 mg/ml. These data suggest that rosemary extract may be suitable as a topical prophylactic or therapeutic agent for herpes viral infections. However, further research is required to elucidate the plant’s active constituents, which may be useful in drug development.
Average motion of emerging solar active region polarities
Authors: Schunker H. , Baumgartner C. , Birch A. C. , Cameron R. H. , Braun D. C. , Gizon L. 
Published: May 2020

Context.The tilt of solar active regions described by Joy’s law is essential for converting a toroidal field to a poloidal field in Babcock-Leighton dynamo models. In thin flux tube models the Coriolis force causes what we observe as Joy’s law, acting on east-west flows as they rise towards the surface.Aims.Our goal is to measure the evolution of the average tilt angle of hundreds of active regions as they emerge, so that we can constrain the origins of Joy’s law.Methods.We measured the tilt angle of the primary bipoles in 153 emerging active regions (EARs) in the Solar Dynamics Observatory Helioseismic Emerging Active Region survey. We used line-of-sight magnetic field measurements averaged over 6 h to define the polarities and measure the tilt angle up to four days after emergence.Results.We find that at the time of emergence the polarities are on average aligned east-west, and that neither the separation nor the tilt depends on latitude. We do find, however, that EARs at higher latitudes have a faster north-south separation speed than those closer to the equator at the emergence time. After emergence, the tilt angle increases and Joy’s law is evident about two days later. The scatter in the tilt angle is independent of flux until about one day after emergence, when we find that higher-flux regions have a smaller scatter in tilt angle than lower-flux regions.Conclusions.Our finding that active regions emerge with an east-west alignment is consistent with earlier observations, but is still surprising since thin flux tube models predict that tilt angles of rising flux tubes are generated below the surface. Previously reported tilt angle relaxation of deeply anchored flux tubes can be largely explained by the change in east-west separation. We conclude that Joy’s law is caused by an inherent north-south separation speed present when the flux first reaches the surface, and that the scatter in the tilt angle is consistent with buffeting of the polarities by supergranulation.
Distinguishing between flaring and nonflaring active regions
Authors: Hazra Soumitra , Sardar Gopal , Chowdhury Partha 
Published: May 2020

Context.Large-scale solar eruptions significantly affect space weather and damage space-based human infrastructures. It is necessary to predict large-scale solar eruptions; it will enable us to protect the vulnerable infrastructures of our modern society.Aims.We investigate the difference between flaring and nonflaring active regions. We also investigate whether it is possible to forecast a solar flare.Methods.We used photospheric vector magnetogram data from the Solar Dynamic Observatory’s Helioseismic Magnetic Imager to study the time evolution of photospheric magnetic parameters on the solar surface. We built a database of flaring and nonflaring active regions observed on the solar surface from 2010 to 2017. We trained a machine-learning algorithm with the time evolution of these active region parameters. Finally, we estimated the performance obtained from the machine-learning algorithm.Results.The strength of some magnetic parameters such as the total unsigned magnetic flux, the total unsigned magnetic helicity, the total unsigned vertical current, and the total photospheric magnetic energy density in flaring active regions are much higher than those of the non-flaring regions. These magnetic parameters in a flaring active region evolve fast and are complex. We are able to obtain a good forecasting capability with a relatively high value of true skill statistic. We also find that time evolution of the total unsigned magnetic helicity and the total unsigned magnetic flux provides a very high ability of distinguishing flaring and nonflaring active regions.Conclusions.We can distinguish a flaring active region from a nonflaring region with good accuracy. We confirm that there is no single common parameter that can distinguish all flaring active regions from the nonflaring regions. However, the time evolution of the top two magnetic parameters, the total unsigned magnetic flux and the total unsigned magnetic helicity, have a very high distinguishing capability.
Understanding Saturn’s interior from theCassiniGrand Finale gravity measurements
Authors: Ni Dongdong 
Published: May 2020

Context.Measurements of Saturn’s gravity field byCassiniGrand Finale have been acquired with high precision. It has been demonstrated that the even gravitational harmonicsJ6–J10have larger absolute values than the predictions by typical rigid-body interior models. A four-layer structure model, proposed to interpret Juno’s gravity measurements for Jupiter, has been applied to Saturn, but great attention was paid to the depth of zonal flows in order to interpret the large absolute values ofJ6–J10.Aims.We aim to understand the internal structure and interior composition of Saturn with a similar model for Jupiter. The additional uncertainties in Saturn’s structure and composition are investigated in detail, such as rotation periods, atmospheric helium mass fractions, and flow-induced gravity corrections. Also, we investigate the effect of equations of state for hydrogen and helium on the predictions of the core mass and heavy element abundance.Methods.In the four-layer structure model, we adjusted the heavy element abundances in the outer two envelopes and the mass of the compact core in order to reproduce Saturn’s equatorial radius as well as theCassiniGrand Finale gravity measurements corrected by the flow-induced gravity signals. Different four-layer interior models are specified in terms of the rotation period, the atmospheric helium mass fraction, and the flow-induced gravity corrections. Two different ab initio equations of state for hydrogen and helium were used in interior structure calculations. Optimized calculations were then performed to explore Saturn’s internal structure and composition.Results.It is found that the absolute values ofJ6–J10tend to increase with increasing deep rotation rate and depend on the equations of state adopted in interior calculations. Saturn’s deep rotation rate and atmospheric helium mass fraction are important to determine the distribution of helium and heavy elements in the outer envelopes. We also show that the core mass and heavy element abundance in Saturn are dependent upon the deep rotation rate, the atmospheric helium mass fraction, the flow-induced gravity corrections, and the equations of state for hydrogen and helium.
Das Druckschmerz-Manual
Authors: Corts Magga 
Published: May 2020

SummaryDruckschmerzen können sowohl durch mechanischen Druck ausgelöst werden als auch von innen durch überschwelliges Gewebe entstehen, welches benachbartes Gewebe komprimiert. Je nach Pathologie lassen sich verschiedene Bereiche des Körpers manuell auf Druckdolenzen, also mechanisch ausgelöste Druckschmerzen, hin untersuchen. Druckschmerzen sind als Hinweiszeichen zu verstehen; entsprechende Verdachtsdiagnosen müssen mit weiteren diagnostischen Mitteln gesichert werden.
Dynamical processes of interstitial diffusion in a two-dimensional colloidal crystal
Authors: Kim Sung-Cheol , Yu Lichao , Pertsinidis Alexandros , Ling Xinsheng Sean 
Published: May 2020

Significance
Defects in crystalline materials are of broad and fundamental interest. In condensed-matter physics, defect dynamics contain essential information about the microscopic processes of crystal formation and melting. Two-dimensional melting (2D) is widely accepted to be mediated by the proliferation of edge dislocations. In 2D crystals, vacancies and interstitials are, in fact, bound pairs of edge dislocations and disclinations. They are expected to play critical roles in 2D melting. We demonstrated significant progress in quantifying the dynamical processes of interstitials. We also propose a simple yet powerful method in visualizing the time-averaged configurations of the defects, providing a direct tool to assess whether the detailed balance is obeyed or violated in the fluctuating processes in a lattice.
Methodological issues in contrastive lexical bundle research
Authors: Pan Fan , Reppen Randi , Biber Douglas 
Published: May 2020

AbstractThis study explores the influence of corpus design when comparing lexical bundle use across groups, examining how the number of texts and average length of texts can impact conclusions about group differences. The study compares the use of lexical bundles by L1-English versus L2-English writers, based on analysis of two sub-corpora of academic articles that are matched for discipline, writer expertize, time of publication, and audience. However, the two sub-corpora differ with respect to the number of texts and the average length of texts. Three experiments examined the influence of differences in corpus composition. The results show that differences in the number of words and number of texts across sub-corpora can have a strong effect on claimed differences in bundle use across groups. This effect is found even when the texts in the corpora are closely matched for their register and topic.