bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced C/EBPs binding to C>T mismatches facilitates fixation of CpG mutations
Authors: Ershova Anna S. , Eliseeva Irina A. , Nikonov Oleg S. , Fedorova Alla D. , Vorontsov Ilya E. , Papatsenko Dmitry , Kulakovskiy Ivan V. 
Published: June 2020

AbstractKnowledge of mechanisms responsible for mutagenesis of adult stem cells is crucial to track genomic alterations that may affect cell renovation and provoke malignant cell transformation. Mutations in regulatory regions are widely studied nowadays, though mostly in cancer. In this study, we decomposed the mutation signature of adult stem cells, mapped the corresponding mutations into transcription factor binding regions, and assessed mutation frequency in sequence motif occurrences. We found binding sites of C/EBP transcription factors strongly enriched with [C>T]G mutations within the core CG dinucleotide related to deamination of the methylated cytosine. This effect was also exhibited in related cancer samples. Structural modeling predicted enhanced CEBPB binding to the consensus sequence with the [C>T]G mismatch, which was then confirmed in the direct experiment. We propose that it is the enhanced binding of C/EBPs that shields C>T transitions from DNA repair and leads to selective accumulation of the [C>T]G mutations within binding sites.
LRRC8A regulates hypotonicity-induced NLRP3 inflammasome activation
Authors: Green Jack P. , Swanton Tessa , Morris Lucy V. , El-Sharkawy Lina Y. , Cook James , Yu Shi , Beswick James , Adamson Antony , Humphreys Neil , Bryce Richard A. , Freeman Sally , Lawrence Catherine , Brough David 
Published: June 2020

AbstractThe NLRP3 inflammasome is a multi-molecular protein complex that converts inactive cytokine precursors into active forms of IL-1β and IL-18. The NLRP3 inflammasome is frequently associated with the damaging inflammation of non-communicable disease states and is considered a therapeutic target. However, there is much regarding the mechanism of NLRP3 activation that remains unknown. Chloride efflux is suggested as an important step in NLRP3 activation, but the identity of which chloride channels are involved is still unknown. We used chemical, biochemical, and genetic approaches to establish the importance of Cl-channels in the regulation of NLRP3 activation. Specifically we identify LRRC8A, an essential component of volume-regulated anion channels (VRAC), as a vital regulator of hypotonicity-induced, but not DAMP-induced, NLRP3 inflammasome activation. Although LRRC8A was dispensable for canonical DAMP-dependent NLRP3 activation, this was still sensitive to Cl-channel inhibitors, suggesting there are additional and specific Cl-sensing and regulating mechanisms controlling NLRP3.
Artificial light at nigh drives early dawn chorus onset times of the Saffron Finch (Sicalis flaveola) in an Andean city
Authors: Marín Gómez Oscar Humberto 
Published: June 2020

AbstractUrban birds around the world have to cope with dominant city stressors as anthropogenic noise and artificial light at night by adjusting the temporal and spectral traits of their acoustic signals. It is widely known that higher anthropogenic noise and artificial light levels can disrupt the morning singing routines, but its influence in tropical urban birds remains poorly explored. Here, I assessed the association between light and noise pollution with the dawn chorus onset of the Saffron Finch (Sicalis flaveola) in an Andean city of Colombia. I studied 32 urban sites distributed in the north of the city, which comprise different conditions of urban development based on the built cover. I annotated the time when the first individual of the Saffron Finch was heard at each site and then I obtained anthropogenic noise and artificial light at night measurements using a smartphone. Findings of this study show that Saffron Finches living in highly developed sites sang earlier at dawn than those occupying less urbanized sites. Unexpectedly this timing difference was related to artificial lighting instead of anthropogenic noise, suggesting that artificial light could drive earlier dawn chorus in a tropical urban bird. Saffron Finches could take advantage of earlier singing for signaling territorial ownership among neighbors, as expected by the social dynamic hypothesis. However, findings of this study should be interpreted carefully because the dawn chorus is a complex phenomenon influenced by many multiple factors. Future studies need to assess the influence of ALAN on the dawn chorus timing of Neotropical urban birds by taking into account the influence of confounding factors related to urbanization as well as meteorological, ecological, and social drivers.
Validation and performance of a quantitative IgG assay for the screening of SARS-CoV-2 antibodies
Authors: Espino Ana M. , Pantoja Petraleigh , Sariol Carlos A. 
Published: June 2020

AbstractThe current COVID-19 epidemic imposed an unpreceded challenge to the scientific community in terms of treatment, epidemiology, diagnosis, social interaction, fiscal policies and many other areas. The development of accurate and reliable diagnostic tools (high specificity and sensitivity) is crucial in the current period, the near future and in the long term. These assays should provide guidance to identify immune presumptive protected persons, potential plasma, and/or B cell donors and vaccine development among others. Also, such assays will be contributory in supporting prospective and retrospective studies to identify the prevalence and incidence of COVID-19 and to characterize the dynamics of the immune response. As of today, only thirteen serological assays have received the Emergency Use Authorization (EUA) by the U.S. Federal Drug Administration (FDA). In this work we describe the development and validation of a quantitative IgG enzyme-linked immunoassay (ELISA) using the recombinant SARS-CoV-2 Spike Protein S1 domain, containing the receptor-binding domain (RBD), showing 98% sensitivity, 98.9% specificity and positive and negative predictive values of 100% and 99.2%, respectively. The assay showed to be useful to test for SARS-CoV-2 IgG antibodies in plasma samples from COVID-19-recovered subjects as potential donors for plasmapheresis. This assay is currently under review by the Federal Drug Administration for an Emergency Use Authorization request (Submission Number EUA201115).
Resin-acid derivatives bind to multiple sites on the voltage-sensor domain of the Saker channel
Authors: Silverå Ejneby Malin , Gromova Arina , Ottosson Nina E , Borg Stina , Estrada-Mondragón Argel , Yazdi Samira , Apostolakis Panagiotis , Elinder Fredrik , Delemotte Lucie 
Published: June 2020

AbstractVoltage-gated potassium (KV) channels can be opened by negatively charged resin acids and their derivatives. These resin acids have been proposed to attract the positively charged voltage-sensor helix (S4) toward the extracellular side of the membrane by binding to a pocket located between the lipid-facing extracellular ends of the transmembrane segments S3 and S4. By contrast to this proposed mechanism, neutralization of the top gating charge of the Shaker KVchannel increased resin-acid induced opening, suggesting other mechanisms and sites of action. Here we explored the binding of two resin-acid derivatives, Wu50 and Wu161, to the activated/open state of the Shaker KVchannel by a combination of in-silico docking, molecular dynamics simulations, and electrophysiology of mutated channels. We identified three potential resin-acid binding sites around S4: (1) The S3/S4 site previously suggested, in which positively charged residues introduced at the top of S4 are critical to keep the compound bound, (2) a site in the cleft between S4 and the pore domain (S4/pore site), in which a tryptophan at the top of S6 and the top gating charge of S4 keeps the compound bound, and (3) a site located on the extracellular side of the voltage-sensor domain, in a cleft formed by S1-S4 (the top-VSD site). The multiple binding sites around S4 and the anticipated helical-screw motion of the helix during activation make the effect of resin-acid derivatives on channel function intricate. The propensity of a specific resin acid to activate and open a voltage-gated channel likely depends on its exact binding dynamics and the types of interactions it can form with the protein in a state-specific manner.eTOC SummarySilverå Ejneby et al use molecular dynamics simulations and electrophysiology to show that the voltage-gated Shaker potassium channel has multiple binding sites for resin-acid derivatives that can regulate its opening.
Harlequin Frogs (Lysapsus) prefer mild places to park
Authors: Ganci Carolina Cunha , Ortega Zaida , Provete Diogo B. 
Published: June 2020

AbstractTemperature affects most aspects of ectotherms’ life history, including physiology and behavior. Studying thermal sensitivity of jumping performance in frogs can help understanding the influence of temperature on different aspects of frog life. Still, studies on the effects of temperature on amphibians are commonly carried out on terrestrial and tree species, creating a gap for aquatic species. We experimentally tested the thermal sensitivity of jumping performance of the Uruguay Harlequin Frog,Lysapsus limellum, assessing three measures: response time, distance of first jump, and total distance travelled. We hypothesized that individuals submitted to extreme temperatures would increase response time, decrease first jump distance, and increase total jump distance. We used an arena with a gradient of air temperature (Ta) ranging from 20 to 40 °C. We placed frogs at different Taand stimulated them to jump. Then, we analysed the influence of Taon the three estimates of jumping performance, using generalized additive models. We found that temperature affected all three measurements of jumping performance, but some relationships were stronger than others. Extreme temperatures increased response time, reduced first jump distance, and increased total distance. The effect was weaker for response time and first jump distance, but substantially stronger for total distance jumped. Although individuals under extreme temperatures experience a reduced jumping performance, they travelled longer distances to find areas with milder temperatures. Thus, we showed thatL. limellumthermoregulates by means of behavior, moving through places at different thermal conditions. Additionally, benefits of displacing to thermally suitable places -in terms of enhanced jumping performance-are bigger than the costs of jumping at reduced locomotor performance, at least under experimental conditions. Our results can help understand how climate change affects the locomotor performance of Neotropical amphibians.
The commitment of barley microspores into embryogenesis involves miRNA-directed regulation of members of the SPL, GRF and HD-ZIPIII transcription factor families
Authors: Bélanger Sébastien , Baldrich Patricia , Lemay Marc-André , Marchand Suzanne , Esteves Patricio , Meyers Blake C. , Belzile François 
Published: June 2020

SUMMARYMicrospore embryogenesis is a model for developmental plasticity and cell fate decisions. To investigate the role of miRNAs in this development, we sequenced sRNAs and the degradome of barley microspores collected prior to (day 0) and after (days 2 and 5) the application of a stress treatment known to induce embryogenesis. Microspores isolated at these timepoints were uniform in both appearance and in their complements of sRNAs. We detected 68 miRNAs in microspores. The abundance of 51 of these miRNAs differed significantly during microspore development. One group of miRNAs was induced when the stress treatment was applied, prior to being repressed when microspores transitioned to embryogenesis. Another group of miRNAs were up-regulated in day-2 microspores and their abundance remained stable or increased in day-5 microspores, a timepoint at which the first clear indications of the transition towards embryogenesis were visible. Collectively, these miRNAs might play a role in the modulation of the stress response, the repression of gametic development, and/or the gain of embryogenic potential. A degradome analysis allowed us to validate the role of miRNAs in regulating 41 specific transcripts. We showed that the transition of microspores toward the embryogenesis pathway involves miRNA-directed regulation of members of theARF, SPL, GRFandHD-ZIPIIItranscription factor families. We noted that 41.5% of these targets were shared between day-2 and day-5 microspores while 26.8% were unique to day-5 microspores. The former set may act to disrupt transcripts involved in pollen development while the latter set may drive the commitment to embryogenesis.
SCIM: Universal Single-Cell Matching with Unpaired Feature Sets
Authors: Stark Stefan G. , Ficek Joanna , Locatello Francesco , Bonilla Ximena , Chevrier Stéphane , Singer Franziska ,   Tumor Profiler Consortium, Rätsch Gunnar , Lehmann Kjong-Van 
Published: June 2020

AbstractMotivationRecent technological advances have led to an increase in the production and availability of single-cell data. The ability to integrate a set of multi-technology measurements would allow the identification of biologically or clinically meaningful observations through the unification of the perspectives afforded by each technology. In most cases, however, profiling technologies consume the used cells and thus pairwise correspondences between datasets are lost. Due to the sheer size single-cell datasets can acquire, scalable algorithms that are able to universally match single-cell measurements carried out in one cell to its corresponding sibling in another technology are needed.ResultsWe propose Single-Cell data Integration via Matching (SCIM), a scalable approach to recover such correspondences in two or more technologies. SCIM assumes that cells share a common (low-dimensional) underlying structure and that the underlying cell distribution is approximately constant across technologies. It constructs a technology-invariant latent space using an auto-encoder framework with an adversarial objective. Multi-modal datasets are integrated by pairing cells across technologies using a bipartite matching scheme that operates on the low-dimensional latent representations. We evaluate SCIM on a simulated cellular branching process and show that the cell-to-cell matches derived by SCIM reflect the same pseudotime on the simulated dataset. Moreover, we apply our method to two real-world scenarios, a melanoma tumor sample and a human bone marrow sample, where we pair cells from a scRNA dataset to their sibling cells in a CyTOF dataset achieving 93% and 84% cell-matching accuracy for each one of the samples respectively.Availabilityhttps://github.com/ratschlab/scim
Neural signatures of pathological hyperdirect pathway activity in Parkinson’s disease
Authors: Oswal Ashwini , Yeh Chien-Hung , Neumann Wolf-Julian , Gratwicke James , Akram Harith , Horn Andreas , Zrinzo Ludvic , Foltynie Tom , Limousin Patricia , Bogacz Rafal , Husain Masud , Brown Peter , Litvak Vladimir 
Published: June 2020

AbstractParkinson’s disease (PD) is characterised by the emergence of pathological patterns of oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between anatomical connectivity and oscillatory synchronisation within this system remains poorly understood. We address this by integrating evidence from invasive electrophysiology, magnetoencephalography, tractography and computational modelling in patients. Coupling between supplementary motor area (SMA) and subthalamic nucleus (STN) within the high beta frequency (21-30 Hz) range correlated with fibre tract densities between these two structures. Additionally within the STN, non-linear waveform features suggestive of cortical synchronisation correlated with cortico-STN fibre densities. Finally, computational modelling revealed that exaggerated hyperdirect cortical inputs to the STN in the upper beta frequency range can provoke the generation of widespread pathological synchrony at lower beta (13-20 Hz) frequencies. These observations reveal a spectral signature of the hyperdirect pathway at high beta frequencies and provide evidence for its pathophysiological role in oscillatory network dysfunction in PD.One sentence summarySignatures of the hyperdirect pathway and its likely role in pathological network disruption in Parkinson’s disease are identified.
Identifying likely transmission pairs with pathogen sequence data using Kolmogorov Forward Equations; an application toM.bovisin cattle and badgers
Authors: Rossi Gianluigi , Crispell Joseph , Balaz Daniel , Lycett Samantha J. , Delahay Richard J. , Kao Rowland R. 
Published: June 2020

AbstractEstablished methods for whole-genome-sequencing (WGS) technology allow for the detection of single-nucleotide polymorphisms (SNPs) in the pathogen genomes sourced from host samples. The information obtained can be used to track the pathogen’s evolution in time and potentially identify ‘who-infected-whom’ with unprecedented accuracy. Successful methods include ‘phylodynamic approaches’ that integrate evolutionary and epidemiological data. However, they are typically computationally intensive, require extensive data, and are best applied when there is a strong molecular clock signal and substantial pathogen diversity.To determine how much transmission information can be inferred when pathogen genetic diversity is low and metadata limited, we propose an analytical approach that combines pathogen WGS data and sampling times from infected hosts. It accounts for ‘between-scale’ processes, in particular within-host pathogen evolution and between-host transmission. We applied this to a well-characterised population with an endemicMycobacterium bovis(the causative agent of bovine/zoonotic tuberculosis, bTB) infection.Our results show that, even with such limited data and low diversity, the computation of the transmission probability between host pairs can help discriminate between likely and unlikely infection pathways and therefore help to identify potential transmission networks, but can be sensitive to assumptions about within-host evolution.
How understudied populations have contributed to our understanding of Alzheimer’s disease genetics
Authors: Dehghani Nadia , Bras Jose , Guerreiro Rita 
Published: June 2020

AbstractThe majority of genome-wide association studies have been conducted using samples with a European genetic background. As a field, we acknowledge this limitation and the need to increase the diversity of populations studied. A major challenge when designing and conducting such studies is to assimilate large samples sizes so that we attain enough statistical power to detect variants associated with disease, particularly when trying to identify variants with low and rare minor allele frequencies. In this study, we aimed to illustrate the benefits, to genetic characterization of Alzheimer’s disease (AD), in researching currently understudied populations. This is important for both fair representation of world populations and the translatability of findings. To that end, we have conducted a literature search to understand the contributions of studies, on different populations, to AD genetics. We systematically quantified the number of studies identifying mutations in known disease-causing genes, in a world-wide manner, and discussed the contributions of research in understudied populations to the identification of novel genetic factors in this disease. Additionally, we compared the effects of genome-wide significant SNPs across populations by focusing on loci that show different association profiles between populations (a key example being APOE). This work functions to both highlight how understudied populations have furthered our understanding of AD genetics, and to help us gage our progress in understanding the genetic architecture of this disease in all populations.
Transdiagnostic dimensions of psychopathology explain individuals’ unique deviations from normative neurodevelopment in brain structure
Authors: Parkes Linden , Moore Tyler M. , Calkins Monica E. , Cook Philip A. , Cieslak Matthew , Roalf David R. , Wolf Daniel H. , Gur Ruben C. , Gur Raquel E. , Satterthwaite Theodore D. , Bassett Danielle S. 
Published: June 2020

ABSTRACTPsychopathology is rooted in neurodevelopment. However, clinical and biological heterogeneity, together with a focus on case-control approaches, have made it difficult to link dimensions of psychopathology to abnormalities of neurodevelopment. Here, using the Philadelphia Neurodevelopmental Cohort, we built normative models of cortical volume and tested whether deviations from these models better predicted psychiatric symptoms compared to raw cortical volume. Specifically, drawing on thep-factorhypothesis, we distilled 117 clinical symptom measures into six orthogonal psychopathology dimensions: overall psychopathology, anxious-misery, externalizing disorders, fear, positive psychotic symptoms, and negative psychotic symptoms. We found that multivariate patterns of deviations yielded improved out-of-sample prediction of psychopathology dimensions compared to multivariate patterns of raw cortical volume. We also found that correlations between overall psychopathology and deviations in ventromedial prefrontal, inferior temporal, dorsal anterior cingulate, and insular cortices were stronger than those observed for specific dimensions of psychopathology (e.g., anxious-misery). Notably, these same regions are consistently implicated in a range of putatively distinct disorders. Finally, we performed conventional case-control comparisons of deviations in a group of individuals with depression and a group with attention-deficit hyperactivity disorder (ADHD). We observed spatially overlapping effects between these groups that diminished when controlling for overall psychopathology. Together, our results suggest that modeling cortical brain features as deviations from normative neurodevelopment improves prediction of psychiatric symptoms in out-of-sample testing, and thatp-factormodels of psychopathology may assist in separating biomarkers that are disorder-general from those that are disorder-specific.
Lef1 expression in fibroblasts maintains developmental potential in adult skin to regenerate wounds
Authors: Phan Quan M. , Fine Gracelyn , Salz Lucia , Herrera Gerardo G. , Wildman Ben , Driskell Iwona M. , Driskell Ryan R. 
Published: June 2020

SummaryScars are a serious health concern that impacts the clinical outcome and long-term well-being of burn victims and individuals with genetic skin conditions associated with wound healing. In this study using mouse as the model, we identify regenerative factors in neonatal skin that will transform adult skin to regenerate instead of repairing wounds with a scar, without perturbing normal development and homeostasis. We utilized single-cell RNA-sequencing (scRNA-seq) to probe unsorted cells from Regenerating, Scarring, Homeostatic, and Developing skin. Our results revealed a transient regenerative cell type in Developing skin, called papillary fibroblasts, which are defined by the expression of a canonical Wnt transcription factor Lef1. Tissue specific ablation of Lef1 inhibited skin regeneration. Importantly, ectopic expression of Lef1 in dermal fibroblasts did not disrupt development and aging, but primed adult skin to undergo enhanced regeneration. Here, we reveal the possibility of transferring the regenerative abilities of neonatal skin to adult tissue by expressing Lef1 in dermal fibroblasts. Finally, we have generated an expandable web resource with a search function to display gene expression in the context of our scRNA-seq data (https://skinregeneration.org/).