bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a remote mutation from the contact paratope on the structure of CDR-H3 in the anti-HIV neutralizing antibody PG16
Authors: Kondo Hiroko X. , Kiribayashi Ryo , Kuroda Daisuke , Kohda Jiro , Kugimiya Akimitsu , Nakano Yasuhisa , Tsumoto Kouhei , Takano Yu 
Published: December 2019

AbstractPG16 is a broadly neutralizing antibody to the human immunodeficiency virus (HIV). A crystal structure of PG16 revealed that the unusually long 28-residue complementarity determining region (CDR) H3 forms a unique subdomain, referred to as a “hammerhead”, that directly contacts the antigen. The hammerhead apparently governs the function of PG16 while a previous experimental assay showed that the mutation of TyrH100Q to Ala, which does not directly contact the antigen, decreased the neutralization ability of PG16. However, the molecular mechanism by which a remote mutation from the hammerhead or contact paratope affects the neutralization potency has remained unclear. Here, we performed molecular dynamics simulations of the wild-type and variants (TyrH100Q to Ala, and TyrH100Q to Phe) of PG16, to clarify the effects of these mutations on the dynamics of CDR-H3. Our simulations revealed that the structural rigidity of the CDR-H3 in PG16 is attributable to the hydrogen bond interaction between TyrH100Q and ProH99, as well as the steric support by TyrH100Q. The loss of both interactions increases the intrinsic fluctuations of the CDR-H3 in PG16, leading to a conformational transition of CDR-H3 toward an inactive state.
Small molecule allosteric uncoupling of microtubule depolymerase activity from motility in human Kinesin-5 during mitotic spindle assembly
Authors: Kim Catherine D. , Kim Elizabeth D. , Liu Liqiong , Buckley Rebecca S. , Parameswaran Sreeja , Kim Sunyoung , Wojcik Edward J. 
Published: December 2019

AbstractHuman Kinesin-5 (Eg5) has a large number of known allosteric inhibitors that disrupt its mitotic function. Small-molecule inhibitors of Eg5 are candidate anti-cancer agents and important probes for understanding the cellular function. Here we show that Eg5 is capable of more than one type of microtubule interaction, and these activities can be controlled by allosteric agents. While both monastrol and S-trityl-L-cysteine inhibit Eg5 motility, our data reveal an unexpected ability of these loop5 targeting inhibitors to differentially control a novel Eg5 microtubule depolymerizing activity. Remarkably, small molecule loop5 effectors are able to independently modulate discrete functional interactions between the motor and microtubule track. We establish that motility can be uncoupled from the microtubule depolymerase activity and argue that loop5-targeting inhibitors of Kinesin-5 should not all be considered functionally synonymous. Also, the depolymerizing activity of the motor does not contribute to the genesis of monopolar spindles during allosteric inhibition of motility, but instead reveals a new function. We propose that, in addition to its canonical role in participating in the construction of the three-dimensional mitotic spindle structure, Eg5 also plays a distinct role in regulating the dynamics of individual microtubules, and thereby impacts the density of the mitotic spindle.
Recursive patterns in online echo
chambers
Authors: Brugnoli Emanuele , Cinelli Matteo , Quattrociocchi Walter , Scala Antonio 
Published: December 2019

AbstractDespite their entertainment oriented purpose, social
media changed the way users access information, debate, and form
their opinions. Recent studies, indeed, showed that users online
tend to promote their favored narratives and thus to form polarized
groups around a common system of beliefs. Confirmation bias helps to
account for users’ decisions about whether to spread content, thus
creating informational cascades within identifiable communities. At
the same time, aggregation of favored information within those
communities reinforces selective exposure and group polarization.
Along this path, through a thorough quantitative analysis we
approach connectivity patterns of 1.2 M Facebook users engaged with
two very conflicting narratives: scientific and conspiracy news.
Analyzing such data, we quantitatively investigate the effect of two
mechanisms (namely challenge avoidance and reinforcement seeking)
behind confirmation bias, one of the major drivers of human behavior
in social media. We find that challenge avoidance mechanism triggers
the emergence of two distinct and polarized groups of users (i.e.,
echo chambers) who also tend to be surrounded by friends having
similar systems of beliefs. Through a network based approach, we
show how the reinforcement seeking mechanism limits the influence of
neighbors and primarily drives the selection and diffusion of
contents even among like-minded users, thus fostering the formation
of highly polarized sub-clusters within the same echo chamber.
Finally, we show that polarized users reinforce their preexisting
beliefs by leveraging the activity of their like-minded neighbors,
and this trend grows with the user engagement suggesting how peer
influence acts as a support for reinforcement seeking.
Electromagnetic field quantization and quantum optical input-output relation for grating
Authors: Wang Tiecheng 
Published: December 2019

AbstractA quantization scheme is developed for the radiation and higher order electromagnetic fields in one dimensional periodic, dispersive and absorbing dielectric medium. For this structure, the Green function is solved based on the plane wave expansion method, thus the photon operators, commutation relations and quantum Langevin equations are given and studied based on the Green function approach, moreover, the input-output relations are also derived. It is proved that this quantum theory can be reduced back to that of the predecessors’ study on the homogenous dielectric. Based on this method, we find that the transformation of the photon state through the lossy grating is non-unitary and that the notable non-unitary transformation can be obtained by tuning the imaginary part of the permittivity, we also discussed the excellent quantum optical properties for the grating which are similar to the classical optical phenomena. We believe our work is very beneficial for the control and regulation of the quantum light based on gratings.
Relationship of extracellular volume assessed on cardiac magnetic resonance and serum cardiac troponins and natriuretic peptides with heart failure outcomes
Authors: Yang Eric Y. , Khan Mohammad A. , Graviss Edward A. , Nguyen Duc T. , Bhimaraj Arvind , Nambi Vijay , Hoogeveen Ron C. , Ballantyne Christie M. , Zoghbi William A. , Shah Dipan J. 
Published: December 2019

AbstractMeasures of serum cardiac troponins and natriuretic peptides have become established as prognostic heart failure risk markers. In addition to detecting myocardial fibrosis through late gadolinium enhancement (LGE), extracellular volume fraction (ECV) measures by cardiac magnetic resonance (CMR) have emerged as a phenotypic imaging risk marker for incident heart failure outcomes. We sought to examine the relationship between cardiac troponins, natriuretic peptides, ECV and their associations with incident heart failure events in a CMR referral base. Mid short axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. Global ECV was derived from T1 maps using the area-weighted average of only LGE-absent segments. ECV was considered elevated if measured >30%, the upper 95% bounds of a reference healthy group without known cardiac disease (n = 28). Patients were dichotomized by presence of elevated ECV. High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal B-type natriuretic peptide (NT-proBNP) were measured using serum samples acquired and stored at time of CMR scan, and patients were categorized into 3 groups for each blood marker based on recommended cutoff values. Subsequent heart failure admission and any death were ascertained. Relationships with ECV, hs-cTnT, and NT-proBNP were examined separately and as a composite with Cox proportional hazard models. Of 1,604 serial patients referred for a clinical CMR with myocardial T1 maps, 331 were eligible after exclusions and had blood available and were followed over a median 25.0 [interquartile range 21.8, 31.7] months. After adjustments for age (mean 57.3 [standard deviation (SD) 15.1 years), gender (61% male), and ethnicity (12.7% black), elevated ECV remained a predictor of a first composite heart failure outcome for patients with high levels of hs-cTnT (≥14 ng/L; hazard ratio [HR] 2.42 [95% confidence interval (CI) 1.17, 5.03]; p = 0.02) and NT-proBNP (≥300 pg/mL; HR 2.28 [95% CI 1.24, 4.29]; p = 0.01). Similar trends were seen for lower category levels of blood markers, but did not persist with minimal covariate adjustments. Elevated measures of ECV by CMR are associated with incident heart failure outcomes in patients with high hs-cTnT and NT-proBNP levels. This imaging marker may have a role for additional heart failure risk stratification.
Acute pancreatitis promotes the generation of two different exosome populations
Authors: Jiménez-Alesanco A. , Marcuello M. , Pastor-Jiménez M. , López-Puerto L. , Bonjoch L. , Gironella M. , Carrascal M. , Abian J. , de-Madaria E. , Closa D. 
Published: December 2019

AbstractExosomes are small extracellular vesicles that act as intercellular messengers. Previous studies revealed that, during acute pancreatitis, circulating exosomes could reach the alveolar compartment and activate macrophages. However, proteomic analysis suggested that the most likely origin of these exosomes could be the liver instead of the pancreas. The present study aimed to characterize the exosomes released by pancreas to pancreatitis-associated ascitic fluid (PAAF) as well as those circulating in plasma in an experimental model of taurocholate-induced acute pancreatitis in rats. We provide evidence that during acute pancreatitis two different populations of exosomes are generated with relevant differences in cell distribution, protein and microRNA content as well as different implications in their physiological effects. During pancreatitis plasma exosomes, but not PAAF exosomes, are enriched in the inflammatory miR-155 and show low levels of miR-21 and miR-122. Mass spectrometry-based proteomic analysis showed that PAAF exosomes contains 10–30 fold higher loading of histones and ribosomal proteins compared to plasma exosomes. Finally, plasma exosomes have higher pro-inflammatory activity on macrophages than PAAF exosomes. These results confirm the generation of two different populations of exosomes during acute pancreatitis. Deep understanding of their specific functions will be necessary to use them as therapeutic targets at different stages of the disease.
Molecular serotype-specific identification of Streptococcus pneumoniae using loop-mediated isothermal amplification
Authors: Takano Chika , Kuramochi Yoko , Seki Mitsuko , Kim Dong Wook , Omagari Daisuke , Sasano Mari , Chang Bin , Ohnishi Makoto , Kim Eun Jin , Fuwa Kazumasa , Kilgore Paul E. , Hoshino Tomonori , Hayakawa Satoshi 
Published: December 2019

AbstractIn children, the incidence of pneumococcal meningitis has decreased since the introduction of pneumococcal conjugate vaccine (PCV7 and PCV13). However, since the introduction of the vaccine, developed countries have seen the emergence of non-PCV13 serotypes. However, invasive pneumococcal disease (IPD) caused by PCV13-targeted serotypes still represents an important public health problem in resource-limited countries. To develop a rapid, simple, and cost-effective assay to detect serotypes ofStreptococcus pneumoniae, we developed a novel loop-mediated isothermal amplification (LAMP) assay based on the sequences available for the 13 capsular types that are included in PCV13: 1, 3, 4, 5, 6 A, 6B, 7 F, 9 V, 14, 18 C, 19 A, 19 F, and 23 F. We evaluated test reactivity, specificity, sensitivity and performance, and compared the results between established LAMP and conventional PCR assays. To support its clinical use, the detection limits of the LAMP assay were evaluated using bacterial genomic DNA-spiked cerebrospinal fluid (CSF) and blood specimens. We confirmed the specificity of the LAMP assay using 41 serotypes of pneumococcal strains. The sensitivity of the LAMP assay was 10 to 100 copies per reaction, compared to 10 to 104copies per reaction for PCR assays. The detection limits of the LAMP assay were comparable when using DNA-spiked CSF and blood specimens, as compared to using purified DNA as the template. In conclusion, a rapid and simple LAMP-based pneumococcal serotyping method has been developed. This is the first report of a LAMP method for a PCV13 serotype-specific identification assay, which could be a promising step to facilitate epidemiological studies of pneumococcal serotyping.
Extensive recombination challenges the utility of Sugarcane mosaic virus phylogeny and strain typing
Authors: Braidwood Luke , Müller Sebastian Y. , Baulcombe David 
Published: December 2019

AbstractSugarcane mosaic virus (SCMV) is distributed worldwide and infects three major crops: sugarcane, maize, and sorghum. The impact of SCMV is increased by its interaction with Maize chlorotic mottle virus which causes the synergistic maize disease maize lethal necrosis. Here, we characterised maize lethal necrosis-infected maize from multiple sites in East Africa, and found that SCMV was present in all thirty samples. This distribution pattern indicates that SCMV is a major partner virus in the East African maize lethal necrosis outbreak. Consistent with previous studies, our SCMV isolates were highly variable with several statistically supported recombination hot- and cold-spots across the SCMV genome. The recombination events generate conflicting phylogenetic signals from different fragments of the SCMV genome, so it is not appropriate to group SCMV genomes by simple similarity.
Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort
Authors: van Laarhoven Constance J. H. C. M. , van Setten Jessica , van Herwaarden Joost A. , Pasterkamp Gerard , de Kleijn Dominique P. V. , de Borst Gert J. , van der Laan Sander W. 
Published: December 2019

AbstractRecent genome-wide association studies (GWAS) have discovered ten genetic risk variants for abdominal aortic aneurysms (AAA). To what extent these genetic variants contribute to the pathology of aneurysms is yet unknown. The present study aims to investigate whether genetic risk variants are associated with three clinical features: diameter of aneurysm sac, type of artery and aneurysm related-symptoms in aortic and peripheral aneurysm patients. Aneurysm tissue of 415 patients included in the Aneurysm-Express biobank was used. A best-fit polygenic risk score (PRS) based on previous GWAS effect estimates was modeled for each clinical phenotype. The best-fit PRS (including 272 variants at PT = 0.01015) showed a significant correlation with aneurysm diameter (R2 = 0.019, p = 0.001). No polygenic association was found with clinical symptoms or artery type. In addition, the ten genome-wide significant risk variants for AAA were tested individually, but no associations were observed with any of the clinical phenotypes. All models were corrected for confounders and data was normalized. In conclusion, a weighted PRS of AAA susceptibility explained 1.9% of the phenotypic variation (p = 0.001) in diameter in aneurysm patients. Given our limited sample size, future biobank collaborations need to confirm a potential causal role of susceptibility variants on aneurysmal disease initiation and progression.
Plant-mediated effects of ozone on herbivores depend on exposure duration and temperature
Authors: Duque Laura , Poelman Erik H. , Steffan-Dewenter Ingolf 
Published: December 2019

AbstractAbiotic stress by elevated tropospheric ozone and temperature can alter plants’ metabolism, growth, and nutritional value and modify the life cycle of their herbivores. We investigated how the duration of exposure of Sinapis arvensis plants to high ozone and temperature levels affect the life cycle of the large cabbage white, Pieris brassicae. Plants were exposed to ozone-clean (control) or ozone-enriched conditions (120 ppb) for either 1 or 5 days and were afterwards kept in a greenhouse with variable temperature conditions. When given the choice, P. brassicae butterflies laid 49% fewer eggs on ozone-exposed than on control plants when the exposure lasted for 5 days, but showed no preference when exposure lasted for 1 day. The caterpillars took longer to hatch on ozone-exposed plants and at lower ambient temperatures. The ozone treatment had a positive effect on the survival of the eggs. Ozone decreased the growth of caterpillars reared at higher temperatures on plants exposed for 5 days, but not on plants exposed for 1 day. Overall, longer exposure of the plants to ozone and higher temperatures affected the life cycle of the herbivore more strongly. With global warming, the indirect impacts of ozone on herbivores are likely to become more common.
In Silico Models of DNA Damage and Repair in Proton Treatment Planning: A Proof of Concept
Authors: Smith Edward A. K. , Henthorn N. T. , Warmenhoven J. W. , Ingram S. P. , Aitkenhead A. H. , Richardson J. C. , Sitch P. , Chadwick A. L. , Underwood T. S. A. , Merchant M. J. , Burnet N. G. , Kirkby N. F. , Kirkby K. J. , Mackay R. I. 
Published: December 2019

AbstractThere is strong in vitro cell survival evidence that the relative biological effectiveness (RBE) of protons is variable, with dependence on factors such as linear energy transfer (LET) and dose. This is coupled with the growing in vivo evidence, from post-treatment image change analysis, of a variable RBE. Despite this, a constant RBE of 1.1 is still applied as a standard in proton therapy. However, there is a building clinical interest in incorporating a variable RBE. Recently, correlations summarising Monte Carlo-based mechanistic models of DNA damage and repair with absorbed dose and LET have been published as the Manchester mechanistic (MM) model. These correlations offer an alternative path to variable RBE compared to the more standard phenomenological models. In this proof of concept work, these correlations have been extended to acquire RBE-weighted dose distributions and calculated, along with other RBE models, on a treatment plan. The phenomenological and mechanistic models for RBE have been shown to produce comparable results with some differences in magnitude and relative distribution. The mechanistic model found a large RBE for misrepair, which phenomenological models are unable to do. The potential of the MM model to predict multiple endpoints presents a clear advantage over phenomenological models.
Up-regulated fibronectin in 3D culture facilitates spreading of triple negative breast cancer cells on 2D through integrin β-5 and Src
Authors: Park Hwa -Jeong , Helfman David M. 
Published: December 2019

AbstractUsing MDA-MB-231 cells as a model of triple negative breast cancer (TNBC) and its metastatic sub-cell lines that preferentially metastasize to lung, bone or brain, we found that the mRNA and protein levels of fibronectin (FN) are increased in MDA-MB-231 cells and its lung metastatic derivative, when cultivated in three-dimensional (3D) suspension cultures. The increase of FN expression in 3D was dependent on p38 mitogen-activated protein kinase (MAPK) because it was prevented by treatment of cells with SB203580, an inhibitor of p38MAPK. The up-regulated FN was converted into fibrils, and it enhanced cell spreading when cells cultured in 3D were transferred to two-dimensional (2D) culture. The arginine-glycine-aspartate (RGD) peptides and siRNAs targeting of integrin β-5 inhibited spreading of cells regardless of the presence of FN on 2D culture dishes. In addition, the levels of phosphorylated Src were found to be increased in 3D and the treatment of cells with SU6656, an inhibitor of Src, decreased the rate of cell spreading on FN. Collectively, these studies demonstrate that increased cellular FN in 3D suspension culture facilitates cancer cell attachment and spreading via integrin β-5 and Src, suggesting that the increased FN promotes initial attachment of cancer cells to secondary organs after circulation during metastasis.
Fungal and bacterial diversity of Svalbard subglacial ice
Authors: Perini L. , Gostinčar C. , Gunde-Cimerman N. 
Published: December 2019

AbstractThe composition of fungal and bacterial communities in three polythermal glaciers and associated aquatic environments in Kongsfjorden, Svalbard was analysed using a combination of cultivation and amplicon sequencing. 109 fungal strains belonging to 30 mostly basidiomycetous species were isolated from glacial samples with counts up to 103CFU/100 ml.Glaciozyma-related taxon andPhenoliferia psychrophenolicawere the dominant species. Unexpectedly, amplicon sequencing uncovered sequences of Chytridiomycota in all samples and Rozellomycota in sea water, lake water, and tap water. Sequences ofMalassezia restrictaand of the extremely halotolerantHortaea werneckiiwere also found in subglacial habitats for the first time. Overall, the fungal communities within a glacier and among glaciers were diverse and spatially heterogenous. Contrary to this, there was a large overlap between the bacterial communities of different glaciers, withFlavobacteriumsp. being the most frequently isolated. In amplicon sequencing Actinobacteria and Proteobacteria sequences were the most abundant.
Inhibitory cell populations depend on age, sex, and prior experience across a neural network for Critical Period learning
Authors: Gogola Joseph V. , Gores Elisa O. , London Sarah E. 
Published: December 2019

AbstractIn many ways, the complement of cell subtypes determines the information processing that a local brain circuit can perform. For example, the balance of excitatory and inhibitory (E/I) signaling within a brain region contributes to response magnitude and specificity in ways that influence the effectiveness of information processing. An extreme example of response changes to sensory information occur across Critical Periods (CPs). In primary mammalian visual cortex, GAD65 and parvalbumin inhibitory cell types in particular control experience-dependent responses during a CP. Here, we test how the density of GAD65- and parvalbumin-expressing cells may inform on a CP for complex behavioral learning. Juvenile male zebra finch songbirds (females cannot sing) learn to sing through coordinated sensory, sensorimotor, and motor learning processes distributed throughout a well-defined neural network. There is a CP for sensory learning, the process by which a young male forms a memory of his “tutor’s” song, which is then used to guide the young bird’s emerging song structure. We quantified the effect of sex and experience with a tutor on the cell densities of GAD65- and parvalbumin-expressing cells across major nodes of the song network, using ages that span the CP for tutor song memorization. As a resource, we also include whole-brain mapping data for both genes. Results indicate that inhibitory cell populations differ across sex, age, and experiential conditions, but not always in the ways we predicted.