bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ankyrin repeats in context with human population variation
Authors: Utgés Javier S. , Tsenkov Maxim I. , Dietrich Noah J. M. , MacGowan Stuart A. , Barton Geoffrey J. 
Published: May 2021

AbstractAnkyrin protein repeats bind to a wide range of substrates and are one of the most common protein motifs in nature. Here, we collate a high-quality alignment of 7,407 ankyrin repeats and examine for the first time, the distribution of human population variants from large-scale sequencing of healthy individuals across this family. Population variants are not randomly distributed across the genome but are constrained by gene essentiality and function. Accordingly, we interpret the population variants in context with evolutionary constraint and structural features including secondary structure, accessibility and protein-protein interactions across 383 three-dimensional structures of ankyrin repeats. We find five positions that are highly conserved across homologs and also depleted in missense variants within the human population. These positions are significantly enriched in intra-domain contacts and so likely to be key for repeat packing. In contrast, a group of evolutionarily divergent positions are found to be depleted in missense variants in human but significantly enriched in protein-protein interactions. Our analysis also suggests the domain has three, not two surfaces, each with different patterns of enrichment in protein-substrate interactions and missense variants. Our findings will be of interest to those studying or engineering ankyrin-repeat containing proteins as well as those interpreting the significance of disease variants.Author SummaryComparison of variation at each position of the amino acid sequence for a protein across different species is a powerful way to identify parts of the protein that are important for its structure and function. Large-scale DNA sequencing of healthy people has recently made it possible to study normal genetic variation within just one species. Our work combines information on genetic differences between over 100,000 people with in-depth analysis of all available three-dimensional structures for Ankyrin repeats which are a widespread family of binding proteins formed by units with similar amino acid sequence that are found in tandem. Our combined analysis identifies sites critical for ankyrin stability as well as the positions most important for substrate interactions and hence function. Although focused only on the Ankyrins, the principles developed in our work are general and can be applied to any protein family.
An Investigation of Neural Mechanisms Underlying Verb Morphology Deficits in Aphasia
Authors: Pifer Madeline , Brodbeck Christian , Faroqi-Shah Yasmeen 
Published: May 2021

ABSTRACTAgrammatic aphasia is an acquired language disorder characterized by slow, non-fluent speech that include primarily content words. It is well-documented that people with agrammatism (PWA) have difficulty with production of verbs and verb morphology, but it is unknown whether these deficits occur at the single word-level, or are the result of a sentence-level impairment. The first aim of this paper is to determine the linguistic level that verb morphology impairments exist at by using magnetoencephalography (MEG) scanning to analyze neural response to two language tasks (one word-level, and one sentence-level). It has also been demonstrated that PWA benefit from a morphosemantic intervention for verb morphology deficits, but it is unknown if this therapy induces neuroplastic changes in the brain. The second aim of this paper is to determine whether or not neuroplastic changes occur after treatment, and explore the neural mechanisms by which this improvement occurs.
Reconstructing unobserved cellular states from paired single-cell lineage tracing and transcriptomics data
Authors: Ouardini Khalil , Lopez Romain , Jones Matthew G. , Prillo Sebastian , Zhang Richard , Jordan Michael I. , Yosef Nir 
Published: May 2021

AbstractNovel experimental assays now simultaneously measure lineage relationships and transcriptomic states from single cells, thanks to CRISPR/Cas9-based genome engineering. These multimodal measurements allow researchers not only to build comprehensive phylogenetic models relating all cells but also infer transcriptomic determinants of consequential subclonal behavior. The gene expression data, however, is limited to cells that are currently present (“leaves” of the phylogeny). As a consequence, researchers cannot form hypotheses about unobserved, or “ancestral”, states that gave rise to the observed population. To address this, we introduce TreeVAE: a probabilistic framework for estimating ancestral transcriptional states. TreeVAE uses a variational autoencoder (VAE) to model the observed transcriptomic data while accounting for the phylogenetic relationships between cells. Using simulations, we demonstrate that TreeVAE outperforms benchmarks in reconstructing ancestral states on several metrics. TreeVAE also provides a measure of uncertainty, which we demonstrate to correlate well with its prediction accuracy. This estimate therefore potentially provides a data-driven way to estimate how far back in the ancestor chain predictions could be made. Finally, using real data from lung cancer metastasis, we show that accounting for phylogenetic relationship between cells improves goodness of fit. Together, TreeVAE provides a principled framework for reconstructing unobserved cellular states from single cell lineage tracing data.
No evidence of human genome integration of SARS-CoV-2 found by long-read DNA sequencing
Authors: Smits Nathan , Rasmussen Jay , Bodea Gabriela O. , Amarilla Alberto A. , Gerdes Patricia , Sanchez-Luque Francisco J. , Ajjikuttira Prabha , Modhiran Naphak , Liang Benjamin , Faivre Jamila , Deveson Ira W. , Khromykh Alexander A. , Watterson Daniel , Ewing Adam D. , Faulkner Geoffrey J. 
Published: May 2021

SUMMARYA recent study proposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we applied deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2, and did not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolved 78 L1 insertions arisingin vitroin the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV) positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions via ONT sequencing. That we found no evidence of SARS-CoV-2 integration suggests such events are, at most, extremely rarein vivo, and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.
Partitioning the temporal changes in abundance-based beta diversity into loss and gain components
Authors: Tatsumi Shinichi , Iritani Ryosuke , Cadotte Marc W. 
Published: May 2021

ABSTRACTEcologists have long recognized that the losses and gains in local species abundances can either decrease or increase spatial beta diversity, phenomena often referred to as biotic homogenization and differentiation, respectively. However, quantifying such dynamic impacts of species abundances on beta diversity has remained a methodological challenge.Here, we develop a numerical method to additively partition the temporal changes in beta diversity into distinct components that reflect the losses and gains in local species abundances. Our method is based on Ružička and Bray–Curtis indices and the normalized abundance-based Whittaker’s beta diversity. The temporal changes in these measures are partitioned into components that represent biotic homogenization and differentiation driven by abundance losses and gains at both species and community levels.Application of the method to a Swedish fish community dataset revealed decreases in beta diversity between 1990 and 2018. The homogenization of fish communities was explained by gains, but not losses, in species abundances across sites. Species-level partitioning further showed that the homogenization was largely caused by the increased population sizes of a particular species in sites where it was already present.The results highlight that our partitioning method effectively identifies local population and community processes embedded in regional biodiversity patterns. We believe that explicit analyses of the losses and gains in species abundances should bring deeper insights into the dynamics of beta diversity.
Now you see it, now you don’t: optimal parameters for interslice stimulation in concurrent TMS-fMRI
Authors: Scrivener C. L. , Jackson J. B. , Correia M. M. , Mada M. , Woolgar A 
Published: May 2021

AbstractThe powerful combination of transcranial magnetic stimulation (TMS) concurrent with functional magnetic resonance imaging (fMRI) provides rare insights into the causal relationships between brain activity and behaviour. Despite a recent resurgence in popularity, TMS-fMRI remains technically challenging. Here we examined the feasibility of applying TMS during short gaps between fMRI slices to avoid incurring artefacts in the fMRI data. We quantified signal dropout and changes in temporal signal-to-noise ratio (tSNR) for TMS pulses presented at timepoints from 100ms before to 100ms after slice onset. Up to 3 pulses were delivered per volume using MagVenture’s MR-compatible TMS coil. We used a spherical phantom, two 7-channel TMS-dedicated surface coils, and a multiband (MB) sequence (factor=2) with interslice gaps of 100ms and 40ms, on a Siemens 3T Prisma-fit scanner. For comparison we repeated a subset of parameters with a more standard single-channel TxRx (birdcage) coil, and with a human participant and surface coil set up. We found that, even at 100% stimulator output, pulses applied at least - 40ms/+50ms from the onset of slice readout avoid incurring artifacts. This was the case for all three setups. Thus, an interslice protocol can be achieved with a frequency of up to ~10 Hz, using a standard EPI sequence (slice acquisition time: 62.5ms, interslice gap: 40ms). Faster stimulation frequencies would require shorter slice acquisition times, for example using in-plane acceleration. Interslice TMS-fMRI protocols provide a promising avenue for retaining flexible timing of stimulus delivery without incurring TMS artifacts.
Ocellar spatial vision in Myrmecia ants
Authors: Penmetcha Bhavana , Ogawa Yuri , Ryan Laura A , Hart Nathan S , Narendra Ajay 
Published: May 2021

AbstractIn addition to the compound eyes insects possess simple eyes known as ocelli. Input from the ocelli modulates optomotor responses, flight-time initiation and phototactic responses, behaviours that are predominantly mediated by the compound eyes. In this study, using pattern electroretinography (pERG), we investigated the contribution of the compound eyes to ocellar spatial vision in the diurnal Australian bull ant, Myrmecia tarsata by measuring the contrast sensitivity and spatial resolving power of the ocellar second-order neurons under various occlusion conditions. Furthermore, in four species of Myrmecia ants active at different times of the day and in European honeybee, Apis mellifera, we characterized the ocellar visual properties when both visual systems were available. Among the ants, we found that the time of activity had no significant effect on ocellar spatial vision. Comparing day-active ants and the honeybee we did not find any significant effect of locomotion on ocellar spatial vision. In M. tarsata, when the compound eyes were occluded, the amplitude of the pERG signal from the ocelli reduced by three times compared to conditions when the compound eyes were available. The signals from the compound eyes maintained the maximum contrast sensitivity of the ocelli as 13 (7.7%), and the spatial resolving power as 0.29 cpd. We conclude that ocellar spatial vison improves significantly with input from the compound eyes, with a noticeably larger improvement in contrast sensitivity than in spatial resolving power.
Parameter exploration improves the accuracy of long-read genome assembly
Authors: Priyam Anurag , Witwicka Alicja , Brahma Anindita , Stolle Eckart , Wurm Yannick 
Published: May 2021

AbstractLong-molecule sequencing is now routinely applied to generate high-quality reference genome assemblies. However, datasets differ in repeat composition, heterozygosity, read lengths and error profiles. The assembly parameters that provide the best results could thus differ across datasets. By integrating four complementary and biologically meaningful metrics, we show that simple fine-tuning of assembly parameters can substantially improve the quality of long-read genome assemblies. In particular, modifying estimates of sequencing error rates improves some metrics more than two-fold. We provide a flexible software, CompareGenomeQualities, that automates comparisons of assembly qualities for researchers wanting a straightforward mechanism for choosing among multiple assemblies.
Adaptive spectroscopic visible-light optical coherence tomography for human retinal oximetry
Authors: Rubinoff Ian , Kuranov Roman V. , Ghassabi Zeinab , Wang Yuanbo , Beckmann Lisa , Miller David A. , Tayebi Behnam , Wollstein Gadi , Ishikawa Hiroshi , Schuman Joel S. , Zhang Hao F. 
Published: May 2021

AbstractAlterations in the retinal oxygen saturation (sO2) and oxygen consumption are associated with nearly all blinding diseases. A technology that can accurately measure retinal sO2has the potential to improve ophthalmology care significantly. Recently, visible-light optical coherence tomography (vis-OCT) showed great promise for noninvasive, depth-resolved measurement of retinal sO2as well as ultra-high resolution anatomical imaging. We discovered that spectral contaminants (SC), if not correctly removed, could lead to incorrect vis-OCT sO2measurements. There are two main types of SCs associated with vis-OCT systems and eye conditions, respectively. Their negative influence on sO2accuracy is amplified in human eyes due to stringent laser power requirements, eye motions, and varying eye anatomies. We developed an adaptive spectroscopic vis-OCT (Ads-vis-OCT) method to iteratively remove both types of SCs. We validated Ads-vis-OCT inex vivobovine blood samples against a blood-gas analyzer. We further validated Ads-vis-OCT in 125 unique retinal vessels from 18 healthy subjects against pulse-oximeter readings, setting the stage for clinical adoption of vis-OCT.
ILORA: A database of alien vascular flora of India
Authors: Pant Vidushi , Patwardhan Chinmay , Patil Kshitij , Bhowmick Amiya Ranjan , Mukherjee Abhishek , Banerjee Achyut Kumar 
Published: May 2021

Abstract1) Biological invasions pose an unprecedented threat to biodiversity and ecosystems at different spatial scales, especially for a biodiversity-rich developing nation like India. While country-level checklists of alien taxa are important, databases having their biological and ecological attributes are of paramount importance for facilitating research activities and developing policy interventions. Such a comprehensive database for alien flora is lacking in India.2) We have curated data for 14 variables related to ecology, biogeography, introduction pathway, socio-economy and distribution of 1747 alien vascular plant species from 22 national and global sources to produce the Indian Alien Flora Information (ILORA) version 1.0 database. This paper describes the detailed methodology of curating these data along with the rationale behind selecting these variables.3) The database, the first of its kind for the Indian alien flora, will provide easy access to high quality data and offer a ready reference to comprehend the existing scenario of alien plant species in the country. The database is dynamic and will be updated regularly. It has a provision to incorporate user submitted data, which will allow increasing the resolution of the database as well as the expansion of its capacity.4) The database is envisaged to become a nationwide collaborative platform for a wide spectrum of stakeholders. It is freely accessible via an online data repository as well as through a dedicated website (https://ilora2020.wixsite.com/ilora2020).
Broadening a SARS-CoV-1 neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution
Authors: Zhao Fangzhu , Yuan Meng , Keating Celina , Shaabani Namir , Limbo Oliver , Joyce Collin , Woehl Jordan , Barman Shawn , Burns Alison , Zhu Xueyong , Ricciardi Michael , Peng Linghang , Smith Jessica , Huang Deli , Briney Bryan , Sok Devin , Nemazee David , Teijaro John R. , Wilson Ian A. , Burton Dennis R. , Jardine Joseph G. 
Published: May 2021

ABSTRACTThe emergence of SARS-CoV-2 underscores the need for strategies to rapidly develop neutralizing monoclonal antibodies that can function as prophylactic and therapeutic agents and to help guide vaccine design. Here, we demonstrate that engineering approaches can be used to refocus an existing neutralizing antibody to a related but resistant virus. Using a rapid affinity maturation strategy, we engineered CR3022, a SARS-CoV-1 neutralizing antibody, to bind SARS-CoV-2 receptor binding domain with >1000-fold improved affinity. The engineered CR3022 neutralized SARS-CoV-2 and provided prophylactic protection from viral challenge in a small animal model of SARS-CoV-2 infection. Deep sequencing throughout the engineering process paired with crystallographic analysis of an enhanced antibody elucidated the molecular mechanisms by which engineered CR3022 can accommodate sequence differences in the epitope between SARS-CoV-1 and SARS-CoV-2. The workflow described provides a blueprint for rapid broadening of neutralization of an antibody from one virus to closely related but resistant viruses.
Effect of SSRI discontinuation on anxiety-like behaviours in mice
Authors: Collins Helen M , Pinacho Raquel , Ozdemir Dersu , Bannerman David M , Sharp Trevor 
Published: May 2021

AbstractBackgroundAbrupt cessation of therapy with a selective serotonin reuptake inhibitor (SSRI) is associated with a discontinuation syndrome, typified by numerous disabling symptoms including anxiety. Surprisingly little is known of the behavioural effect of SSRI discontinuation in animals.AimHere, the effect of SSRI discontinuation on anxiety-like behaviour was systematically investigated in mice.MethodsExperiments were based on a 3-arm experimental design comprising saline, continued SSRI and discontinued SSRI. Mice were assessed 2 days after SSRI discontinuation over a 5 day period using the elevated plus maze (EPM) and other anxiety tests.ResultsAn exploratory experiment found cessation of paroxetine (12 days) was associated with decreased open arm exploration and reduced total distance travelled, in male but not female mice. Follow-up studies confirmed a discontinuation effect on the EPM in male mice after paroxetine (12 days) and also citalopram (12 days). Mice receiving continued paroxetine (but not citalopram) also showed decreased open arm exploration but this was dissociable from effects of discontinuation. The discontinuation response to paroxetine did not strengthen after 28 days treatment but was absent after 7 days treatment. A discontinuation response was not decernable in other anxiety and fear-learning tests applied 3-5 days after treatment cessation. Finally, discontinuation effects on the EPM were typically associated with decreased locomotion on the test. However, separate locomotor testing implicated anxiety-provoked behavioural inhibition rather than a general reduction in motor activity.ConclusionOverall, the current study provides evidence for a short-lasting behavioural discontinuation response to cessation of SSRI treatment in mice.
A cost-effective way to design a two layered cell trapping microfluidic device
Authors: Lázaro-Guevara José M. 
Published: May 2021

AbstractWhen studying cells population, sometimes is necessary to isolate a specific subset to perform a timeline analysis or determinate the evolution on cell progeny. Microfluidic devices are being used for fulfill this function in multiple designs. However, the design and fabrication of this type of devices involve multiple challenges and high cost. Miniaturization tends to be the primarily challenge where those devices below 10um tends to be so expensive that needs special facilities for fabrication, but using techniques as multilayer fabrication those problems can be overcome. In this work are stated techniques (photolithography, soft-lithography) that helps solving that limitations, from using inexpensive materials, to alignment techniques that does not requires high-tech equipment’s, and a practical design for microfluidic cell trapping array. Where multiple cell types could be seeded and trapped in small cluster (varying on cell size) to be retrieved later on in an easy and practical way.
Identification of tissue-specific and common methylation quantitative trait loci in healthy individuals using MAGAR
Authors: Scherer Michael , Gasparoni Gilles , Rahmouni Souad , Shashkova Tatiana , Arnoux Marion , Louis Edouard , Nostaeva Arina , Avalos Diana , Dermitzakis Emmanouil T. , Aulchenko Yurii S. , Lengauer Thomas , Lyons Paul A. , Georges Michel , Walter Jörn 
Published: May 2021

AbstractBackgroundUnderstanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of epigenomic data in the context of disease. There is a need for systematic approaches not only for determining methylation quantitative trait loci (methQTL) but also for discriminating general from cell-type-specific effects.ResultsHere, we present a two-step computational framework MAGAR, which fully supports identification of methQTLs from matched genotyping and DNA methylation data, and additionally the identification of quantitative cell-type-specific methQTL effects. In a pilot analysis, we apply MAGAR on data in four tissues (ileum, rectum, T-cells, B-cells) from healthy individuals and demonstrate the discrimination of common from cell-type-specific methQTLs. We experimentally validate both types of methQTLs in an independent dataset comprising additional cell types and tissues. Finally, we validate selected methQTLs (PON1, ZNF155, NRG2) by ultra-deep local sequencing. In line with previous reports, we find cell-type-specific methQTLs to be preferentially located in enhancer elements.ConclusionsOur analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic variants to cell-type-specific epigenomic variation.