bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational ligands to VKORC1s and CYPs. Could they predict new anticoagulant rodenticides?
Authors: Bermejo-Nogales A , Navas J.M. , Coll J 
Published: January 2021

AbstractAnticoagulant-resistance in rodents and anticoagulant off-target effects are some of the world-wide problems of increasing concern. To search for new anticoagulant rodenticide candidates we have computationally explored some of the rat genes previously implicated in resistance to actual anticoagulants. In particular, we searched among hundreds of anticoagulant-similar chemotypes those binding rat wild-type VKORC1 (the best-known anticoagulant target, a Vitamin K-recycling enzyme), VKORC1L1 (a VKORC1-related enzyme), Cytochrome P450 CYP enzymes (some of the most important enzymes implicated in detoxification) and anticoagulant-resistant VKORC1-mutants (to minimize propensity to resistance). Results predicted new VKORC1 leads with binding-scores in the low nM range (high binding-affinities) predicting hydroxycoumarin- and naphtoquinone-like chemotypes. We then selected top-leads with additional high binding-scores to more than three anticoagulant-related CYPs, suggesting minimal detoxification rates and therefore maximal anticoagulation expectatives. A downsized list of top top-leads maintaining VKORC1 low-binding scores to anticoagulant resistant mutants, was finally proposed for experimental validation. The combination of different rat targets for computational studies, could be used to search for unrelated chemotypes, for reduction of off-target environmental anticoagulant impacts, and/or as new tools to explore anticoagulant molecular mechanisms.
MYCN-induced nucleolar stress drives an early senescence-like transcriptional program in hTERT-immortalized RPE cells
Authors: Zanotti Sofia , Vanhauwaert Suzanne , Van Neste Christophe , Olexiouk Volodimir , Van Laere Jolien , Verschuuren Marlies , Mus Liselot M. , Durinck Kaat , Tilleman Laurentijn , Deforce Dieter , Van Nieuwerburgh Filip , Hogarty Michael D. , Decaesteker Bieke , De Vos Winnok H. , Speleman Frank 
Published: January 2021

AbstractMYCNis an oncogenic driver in neural crest-derived neuroblastoma and medulloblastoma. To better understand the early effects of MYCN activation in a neural-crest lineage context, we profiled the transcriptome of immortalized human retina pigment epithelial cells with inducible MYCN activation. Gene signatures associated with elevated MYC/MYCN activity were induced after 24 h of MYCN activation, which attenuated but sustained at later time points. Unexpectedly, MYCN activation was accompanied by reduced cell growth. Gene set enrichment analysis revealed a senescence-like signature with strong induction of p53 and p21 but in the absence of canonical hallmarks of senescence such as beta-galactosidase positivity, suggesting incomplete cell fate commitment. When scrutinizing the putative drivers of this growth attenuation, differential gene expression analysis identified several regulators of nucleolar stress. This process was also reflected by phenotypic correlates such as cytoplasmic granule accrual and nucleolar coalescence. Hence, we propose that the induction of MYCN congests the translational machinery, causing nucleolar stress and driving cells into a transient pre-senescent state. Our findings shed new light on the early events induced by MYCN activation and may help unravelling which factors are required for cells to tolerate unscheduled MYCN overexpression during early malignant transformation.HighlightsActivation of MYCN attenuates proliferation in RPE1 cellsGrowth arrest is associated with an early senescence-like transcriptional signatureTranscriptional and phenotypic evidence of nucleolar stressCDKN1Aupregulation in G2 phase primes cells for faltering in subsequent G1
TheArabidopsisimmune receptor EFR increases resistance to the bacterial pathogensXanthomonasandXylellain transgenic sweet orange
Authors: Mitre Letícia Kuster , Teixeira-Silva Natália Sousa , Rybak Katarzyna , Magalhães Diogo Maciel , de Souza-Neto Reinaldo Rodrigues , Robatzek Silke , Zipfel Cyril , de Souza Alessandra Alves 
Published: January 2021

SummaryPlants employ cell surface receptors to recognize pathogen (or microbe)-associated molecular patterns (PAMPs/MAMPs), which are crucial for immune system activation. The well-studiedArabidopsis thalianaELONGATION FACTOR-TU RECEPTOR (EFR) recognizes the conserved bacterial PAMP EF-Tu, and the derived peptides elf18 and elf26. The interfamily transfer of EFR has been shown to increase disease resistance in several crops, such as tomato, rice, wheat, and potato. Here, we generated sweet orange (Citrus sinensis) transgenic lines expressingEFRto test if it would confer broad-spectrum resistance against two important citrus bacterial diseases: citrus canker and citrus variegated chlorosis (CVC). Independent EFR transgenic lines gained responsiveness to elf18 and elf26 peptides fromXanthomonas citriandXylella fastidiosa, as measured by reactive oxygen species (ROS) production, mitogen-activated protein kinase (MAPK) activation and defense gene expression. Consistently, infection assays showed thatCitrus-EFRtransgenic plants were more resistant to citrus canker and CVC. Our results show that the EFR immune receptor can improve plant immunity in a perennial crop against bacterial pathogens, opening perspectives to engineer durable broad-spectrum disease resistance under field conditions.
A parsimonious model for mass-univariate vertex-wise analysis
Authors: Couvy-Duchesne Baptiste , Zhang Futao , Kemper Kathryn E. , Sidorenko Julia , Wray Naomi R. , Visscher Peter M. , Colliot Olivier , Yang Jian 
Published: January 2021

2.AbstractCovariance between grey-matter measurements can reflect structural or functional brain networks though it has also been shown to be influenced by confounding factors (e.g. age, head size, scanner), which could lead to lower mapping precision (increased size of associated clusters) and create distal false positives associations in mass-univariate vertex-wise analyses. We evaluated this concern by performing state-of-the-art mass-univariate analyses (general linear model, GLM) on traits simulated from real vertex-wise grey matter data (including cortical and subcortical thickness and surface area). We contrasted the results with those from linear mixed models (LMMs), which have been shown to overcome similar issues in omics association studies. We showed that when performed on a large sample (N=8,662, UK Biobank), GLMs yielded large spatial clusters of significant vertices and greatly inflated false positive rate (Family Wise Error Rate: FWER=1, cluster false discovery rate: FDR>0.6). We showed that LMMs resulted in more parsimonious results: smaller clusters and reduced false positive rate (yet FWER>5% after Bonferroni correction) but at a cost of increased computation. In practice, the parsimony of LMMs results from controlling for the joint effect of all vertices, which prevents local and distal redundant associations from reaching significance. Next, we performed mass-univariate association analyses on five real UKB traits (age, sex, BMI, fluid intelligence and smoking status) and LMM yielded fewer and more localised associations. We identified 19 significant clusters displaying small associations with age, sex and BMI, which suggest a complex architecture of at least dozens of associated areas with those phenotypes.
Huygens synchronization of medial septal pacemaker neurons generates hippocampal theta oscillation
Authors: Kocsis Barnabás , Martínez-Bellver Sergio , Fiáth Richárd , Domonkos Andor , Sviatkó Katalin , Barthó Péter , Freund Tamás F. , Ulbert István , Káli Szabolcs , Varga Viktor , Hangya Balázs 
Published: January 2021

AbstractEpisodic learning and memory retrieval are critically dependent on a hippocampal 4-12 Hz oscillatory ‘clock’ signal, the theta oscillation. This clock is largely externally paced, by a network of GABAergic neurons in the medial septum (MS). Theoretical studies suggested a range of hypotheses how this network may achieve theta synchrony; however, experimental evidence is still lacking. By recording multiple single MS neurons and hippocampal local field potential oscillations simultaneously, with both acute and chronically implanted silicon probes, we show that MS pacemaker units oscillate at individual frequencies within the theta range in rodents. Synchronization of MS neuron frequencies, accompanied by an elevation of firing rates, was found to parallel hippocampal theta formation in multiple rodent model systems. This suggests a general mechanism for theta synchronization, akin to the synchronization of weakly coupled pendulum clocks observed by Huygens in the 17thcentury. We optogenetically identified the MS pacemaker units as parvalbumin-expressing GABAergic neurons, while the previously enigmatic MS glutamatergic neurons were mostly theta-activated non-rhythmic cells. Our data were consistent with a network model of partially connected single-compartment inhibitory pacemaker neurons, in which synchronization and de-synchronization in the frequency domain upon waxing and waning tonic excitatory drive was sufficient to toggle MS network output between theta and non-theta states. These results provide experimental and theoretical support to a frequency-synchronization mechanism for pacing hippocampal theta, which may serve as an inspirational prototype for the countless examples of synchronization processes in the central nervous system from Nematoda to Anthropoda to Chordate and Vertebrate phyla.
The limits of evolutionary convergence in sympatry: reproductive interference and historical constraints leading to local diversity in warning traits
Authors: Maisonneuve Ludovic , Elias Marianne , Smadi Charline , Llaurens Violaine 
Published: January 2021

AbstractMutualistic interactions between defended species represent a striking case of evolutionary convergence in sympatry, driven by the increased protection against predators brought by mimicry in warning traits. However, such convergence is often limited: sympatric defended species frequently display different or imperfectly similar warning traits. The phylogenetic distance between sympatric species may indeed prevent evolution towards the exact same signal. Moreover, warning traits are also involved in mate recognition, so that trait convergence might result in heterospecific courtship and mating. Here, we develop a mathematical model to investigate the strength and direction of evolution of warning trait in defended species with different ancestral traits. Specifically, we determine the effect of phenotypic distances between ancestral trait states of sympatric defended species and of costs of heterospecific sexual interactions on imperfect mimicry and trait divergence. Our analytical results confirm that reproductive interference and historical constraints limit the convergence of warning traits, leading to either complete divergence, or imperfect mimicry. Our model reveals that imperfect mimicry evolves only when ancestral trait values differ between species due to historical constraints and highlights the importance of female and predator discriminations in the evolution of such imperfect mimicry. Our study thus provides new predictions on how reproductive interference interacts with historical constraints and may promote the emergence of novel warning traits, enhancing mimetic diversity.
Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies
Authors: Hu Jie , Peng Pai , Wang Kai , Liu Bei-zhong , Fang Liang , Luo Fei-yang , Jin Ai-shun , Tang Ni , Huang Ai-long 
Published: January 2021

ABSTRACTSARS-CoV-2 Spike-specific antibodies contribute the majority of the neutralizing activity in most convalescent human sera. Two SARS-CoV-2 variants, N501Y.V1 (also known as B.1.1.7 lineage or VOC-202012/01) and N501Y.V2 (B.1.351 lineage), reported from the United Kingdom and South Africa, contain several mutations in the receptor binding domain of Spike and are of particular concern. To address the infectivity and neutralization escape phenotypes potentially caused by these mutations, we used SARS-CoV-2 pseudovirus system to compare the viral infectivity, as well as the neutralization activities of convalescent sera and monoclonal antibodies (mAbs) against SARS-CoV-2 variants. Our results showed that N501Y Variant 1 and Variant 2 increase viral infectivity compared to the reference strain (wild-type, WT)in vitro. At 8 months after symptom onset, 17 serum samples of 20 participants (85%) retaining titers of ID50>40 against WT pseudovirus, whereas the NAb titers of 8 samples (40%) and 18 samples (90%) decreased below the threshold against N501Y.V1 and N501Y.V2, respectively. In addition, both N501Y Variant 1 and Variant 2 reduced neutralization sensitivity to most (6/8) mAbs tested, while N501Y.V2 even abrogated neutralizing activity of two mAbs. Taken together the results suggest that N501Y.V1 and N501Y.V2 reduce neutralization sensitivity to some convalescent sera and mAbs.
Feline tooth resorption in a case-control study based on a subpopulation of 944 dentally examined cats from a Finnish questionnaire survey of over 8000 cats
Authors: Vapalahti Katariina , Neittaanmäki Henriikka , Lohi Hannes , Virtala Anna-Maija 
Published: January 2021

AbstractTooth resorption (TR) is one of cats’ most common dental diseases. It is a painful condition characterized by progressive dental destruction, which eventually results in loss of teeth. The aetiology of the TR remains unclear, but associations with old age, breed, other oral and dental diseases, and certain environmental factors have been suspected. In our study, we used part of the data from the extensive feline health and environmental survey of 8115 Finnish cats collected through an online survey targeted at cat owners. We aimed to investigate the characteristics of cats having TR and to study risk factors for TR. Because TR is difficult to detect and, in addition, the feline health survey was very comprehensive and included diagnoses defined by both veterinarians and owners themselves, we limited our study to a subpopulation of cats diagnosed with oral or dental disease by a veterinarian and undergone dental examination or surgery under sedation (n=944).The frequency of veterinary-diagnosed TR was 3.9% in the entire health survey data (316/8115) and increased to 21% in the subpopulation of veterinarian-diagnosed and sedated cats (202/944). We utilized case-control multivariable logistic regression in this subpopulation to determine the risk factors and breed variation of feline TR. The 202 cats diagnosed with TR were defined as TR cases and the 742 cats without TR diagnoses served as controls. Results indicate that the risk of TR increases with age. Dental calculus, gingivitis, and periodontitis were associated with TR. These findings and the interaction of dental calculus with gingivitis and periodontitis might suggest that inflammatory changes caused by dental calculus increase the risk of TR. We found Cornish Rex, European, and Ragdoll at higher risk for TR. Exotic-Persians had lower risk, and Turkish van and Devon Rex had no TR. The observed differences between breeds highlight a genetic contribution. In addition, female cats that had food available constantly had significantly less TR than female cats that had feeding times. The underlying influential reasons for this result remain unexplained in our study.
Effect of hydroxyapatite microspheres, amoxicillin-hydroxyapatite and collagen-hydroxyapatite composites on human dental pulp-derived mesenchymal stem cells
Authors: Pupo Yasmine Mendes , Leite Lidiane Maria Boldrini , Senegaglia Alexandra Cristina , Antunes Lisiane , Nadal Jessica Mendes , de Lara Eliane Leal , Saito Rafael Eiji , Antunes Sandra Regina Masetto , Farago Paulo Vitor 
Published: January 2021

AbstractThe aim of this study was to evaluate the in vitro behavior of human dental pulp mesenchymal stem cells (hDPSCs) cultured on scaffolds of three hydroxyapatite-based materials: hydroxyapatite microspheres [HAp]; amoxicillin-hydroxyapatite composite [Amx-HAp]; and collagen-hydroxyapatite composite [Col-HAp]. These hydroxyapatites (HAps) were synthesized through three methods: microwave hydrothermal, hydrothermal reactor (teflon pouches), and precipitation, respectively. We performed an in vitro experimental study using dental pulp stem cells obtained from samples of third molars and characterized by immunophenotypic analysis. Cells were cultured on scaffolds with osteogenic differentiation medium and were maintained for 21 days. Cytotoxicity analysis and migration assay of hDPSCs were evaluated. Each experiment was performed in triplicate. Data analysis was performed using Kruskal-Wallis test and Dunn’s post-hoc test. After 21 days of induction, no differences in genes expression were observed. hDPSCs highly expressed the collagen IA and the osteonectin at the mRNA, which indicated these genes plays an important role in odontogenesis regardless of induction stimulus. Cytotoxicity assay using hDPSCs demonstrated that Col-HAp group presented a number of non-viable cells statistically lower than the control group (p=0.03). In the migration assay after 24h, biomaterials HAp, Amx-HAp, and Col-HAp revealed the same migration behavior for hDPSCs observed to the positive control. Col-HAp also provided a statistically significant higher migration of hDPSCs than HAp (p=0.02). The migration results in 48h for HAp, Amx-HAp, and Col-HAp was intermediate from those achieved by control groups. There was no statistical difference between positive control and Col-HAp (p>0.05). In general, Col-HAp scaffold showed better features for these dynamic parameters of cell viability and cell migration capacities for hDPSCs, leading to suitable adhesion, proliferation, and differentiation of this osteogenic lineage. These data present high clinical importance because Col-HAp can be used in a wide variety of therapeutic areas, including ridge preservation, minor bone augmentation, and periodontal regeneration.
Hosting sea anemones at the Perhentian reefs of Malaysia: population descriptives and associations with live coral cover
Authors: Versteeg Melissa , Campbell Alanah , Halid Hidayah 
Published: January 2021

AbstractAround the Perhentian Islands, coral reefs have been undergoing degradation, as is reported by coral reef monitoring programmes. Current coral reef surveys around the Perhentian Islands do not specifically monitor hosting sea anemone populations, nor do they include investigation of how sea anemone abundance correlates to live coral cover on reef sites. As sea anemones can compete with corals for suitable substrate, nutrients, and light availability, the current study was designed to explore hosting sea anemone abundance and distribution patterns around the Perhentian Islands, as well as assess the presence of significant correlations between sea anemone abundance and live coral cover. Two sites with hosting sea anemone populations were assessed, and data was collected for sea anemone species, formation type, hosting status, and resident Amphiprion species. Additionally, live coral cover estimates were calculated and tested for associations between coral and sea anemone abundance. In total, 403 hosting sea anemone formations were analysed. Statistical analyses revealed that at the research site Village Reef, sea anemones that were actively hosting were larger, and more often encountered in clustered formations. In addition, sea anemone cover was significantly negatively correlated to live coral cover. At research site Teluk Keke, actively hosting sea anemones were also larger, but no other tests revealed significant results at this site. The current study offers a first population analysis of hosting sea anemone assemblages around the Perhentian Islands and provides a preliminary exploration of the associations between hosting sea anemone presence and live coral cover on these reefs.
Binaural (pre)processing for contralateral sound field attenuation and improved speech-in-noise recognition
Authors: Lopez-Poveda Enrique A. , Eustaquio-Martín Almudena , San Victoriano Fernando Martín 
Published: January 2021

ABSTRACTUnderstanding speech presented in competition with other sound sources can be challenging. Here, we reason that this task can be facilitated by improving the signal-to-noise ratio (SNR) in either of the two ears and that in free-field listening scenarios, this can be achieved by attenuating contralateral sounds. We present a binaural (pre)processing algorithm that improves the SNR in the ear ipsilateral to the target sound source by linear subtraction of the weighted contralateral stimulus. Although the weight is regarded as a free parameter, we justify setting it equal to the ratio of ipsilateral to contralateral head-related transfer functions averaged over an appropriate azimuth range. The algorithm is implemented in the frequency domain and evaluated technically and experimentally for normal-hearing listeners in simulated free-field conditions. Results show that (1) it can substantially improve the SNR (up to 20 dB) and the short-term intelligibility metric in the ear ipsilateral to the target source, particularly for speech-like maskers; (2) it can improve speech reception thresholds for sentences in competition with speech-shaped noise by up to 8.5 dB in bilateral listening and 10.0 dB in unilateral listening; (3) it hardly affects sound-source localization; and (4) the improvements, and the algorithm’s directivity pattern depend on the weights. The algorithm accounts qualitatively for binaural unmasking for speech in competition with multiple maskers and for multiple target-masker spatial arrangements, an unexpected property that can inspire binaural intelligibility models.
Effect of landscape heterogeneity on diurnal raptor community richness and diversity in JammuShiwaliks, Jammu and Kashmir
Authors: Kumar Sudesh , Sohil Asha , Ahmed Muzaffar , Sharma Neeraj 
Published: January 2021

AbstractIn this study, we examined the richness and diversity of diurnal raptors along with their foraging guilds across different land uses in a sub-tropical landscape during December 2016 to November 2018. A total of 80 vantage points, 19 line transects and 36 road transects were sampled in 33 sites in six different habitat types in the study area where we recorded 3409 individuals of 29 diurnal raptors in 2 orders and 3 families. Significant variation in bird abundance was observed among different habitat types, farmlands being more specious followed by pure forests, water bodies and forest-farmland interfaces. Among the seasons, summers recorded higher abundance followed by winter, monsoon and post-monsoon. A low diversity value (H′=2.22) however was observed for the whole study area with mean monthly highest recorded during February (H′=2.44) and least during June (H′=1.85). Most of the raptors observed for their food types and foraging were predators (n=22) and rest were carrion feeders (n=22). Fourteen among all observed diurnal raptors were winter visitors and 13 residents with 9 reported globally threatened. A moderately high richness of diurnal raptors substantiate high conservation value of these habitats especially the forest patches and farmlands and thus calls for effective management strategies for the conservation and proliferation of raptors in sub-tropical areas of Jammu region.