bluuebunny/crossref_metadata_2025_split huggingface dataset:
Definition, modeling and detection of saccades in the face of post-saccadic oscillations
Authors: Schweitzer Richard , Rolfs Martin 
Published: March 2021

AbstractWhen analyzing eye tracking data, one of the central tasks is the detection of saccades. Although many automatic saccade detection algorithms exist, the field still debates how to deal with brief periods of instability around saccade offset, so-called post-saccadic oscillations (PSOs), which are especially prominent in today’s widely used video-based eye tracking techniques. There is good evidence that PSOs are caused by inertial forces that act on the elastic components of the eye, such as the iris or the lens. As this relative movement can greatly distort estimates of saccade metrics, especially saccade duration and peak velocity, video-based eye tracking has recurrently been considered unsuitable for measuring saccade kinematics. In this chapter, we review recent biophysical models that describe the relationship between pupil motion and eyeball motion. We found that these models were well capable of accurately reproducing saccade trajectories and implemented a framework for the simulation of saccades, PSOs, and fixations, which can be used – just like datasets hand-labelled by human experts – to evaluate detection algorithms and train statistical models. Moreover, as only pupil and corneal-reflection signals are observable in video-based eye tracking, one may also be able to use these models to predict the unobservable motion of the eyeball. Testing these predictions by analyzing saccade data that was registered with video-based and search-coil eye tracking techniques revealed strong relationships between the two types of measurements, especially when saccade offset is defined as the onset of the PSO. To enable eye tracking researchers to make use of this definition, we present and evaluate two novel algorithms – one based on eye-movement direction inversion, one based on linear classifiers previously trained on simulation data. These algorithms allow for the detection of PSO onset with high fidelity. Even though PSOs may still pose problems for a range of eye tracking applications, the techniques described here may help to alleviate these.
Building alternative consensus trees and supertrees usingk-means and Robinson and Foulds distance
Authors: Tahiri Nadia , Fichet Bernard , Makarenkov Vladimir 
Published: March 2021

AbstractEach gene has its own evolutionary history which can substantially differ from the evolutionary histories of other genes. For example, some individual genes or operons can be affected by specific horizontal gene transfer and recombination events. Thus, the evolutionary history of each gene should be represented by its own phylogenetic tree which may display different evolutionary patterns from the species tree that accounts for the main patterns of vertical descent. The output of traditional consensus tree or supertree inference methods is a unique consensus tree or supertree. Here, we describe a new efficient method for inferring multiple alternative consensus trees and supertrees to best represent the most important evolutionary patterns of a given set of phylogenetic trees (i.e. additive trees orX-trees). We show how a specific version of the populark-means clustering algorithm, based on some interesting properties of the Robinson and Foulds topological distance, can be used to partition a given set of trees into one (when the data are homogeneous) or multiple (when the data are heterogeneous) cluster(s) of trees. We adapt the popular Caliński-Harabasz, Silhouette, Ball and Hall, and Gap cluster validity indices to tree clustering withk-means. A special attention is paid to the relevant but very challenging problem of inferring alternative supertrees, built from phylogenies constructed for different, but mutually overlapping, sets of taxa. The use of the Euclidean approximation in the objective function of the method makes it faster than the existing tree clustering techniques, and thus perfectly suitable for the analysis of large genomic datasets. In this study, we apply it to discover alternative supertrees characterizing the main patterns of evolution of SARS-CoV-2 and the related betacoronaviruses.
Tradeoffs for a viral mutant with enhanced replication speed
Authors: Lanahan Matthew R. , Pfeiffer Julie K. 
Published: March 2021

AbstractRNA viruses exist as genetically heterogeneous populations due to high mutation rates and many of these mutations reduce fitness and/or replication speed. However, it is unknown whether mutations can increase replication speed of a virus already well adapted to replication in cultured cells. By sequentially passaging coxsackievirus B3 in cultured cells and collecting the very earliest progeny, we selected for increased replication speed. We found that a single mutation in a viral capsid protein, VP1-F106L, was sufficient for the fast-replication phenotype. Characterization of this mutant revealed quicker genome release during entry compared to wild-type virus, highlighting a previously unappreciated infection barrier. However, this mutation also reduced capsid stabilityin vitroand reduced replication and pathogenesis in mice. These results reveal a tradeoff between overall replication speed and fitness. Importantly, this approach— selecting for the earliest viral progeny—could be applied to a variety of viral systems and has the potential to reveal unanticipated inefficiencies in viral replication cycles.SignificanceViruses have characteristic replication speeds within a given cell type. Many factors can slow the rate of viral replication, including attenuating mutations and host antiviral responses. However, it has been unclear whether it would be possible to “speed up” a virus that already replicates efficiently in a specific cell type. Here, we selected for a mutant coxsackievirus with enhanced replication speed by sequentially harvesting the very earliest progeny in multiple rounds of selection. A single mutation conferred the fast replication phenotype. While this mutant virus has enhanced replication in cultured cells due to faster genome uncoating, it was attenuated in mice. These results highlight selective pressures that shape viral populations in different environments.
Lateralized deficits in arousal processing after insula lesions: behavioral and autonomic evidence
Authors: Holtmann Olga , Franz Marcel , Moenig Constanze , Tenberge Jan-Gerd , Schloßmacher Insa , Ivanova Iskrena , Preul Christoph , Schwindt Wolfram , Melzer Nico , Miltner Wolfgang H.R. , Straube Thomas 
Published: March 2021

AbstractA large body of evidence ascribes a pivotal role in emotion processing to the insular cortex. However, the complex structure and lateralization of emotional deficits following insular damage are not understood. Here, we investigated emotional ratings of valence and arousal and skin conductance responses (SCR) to a graded series of emotionally arousing scenes in patients with left (n= 10) or right (n= 9) insular damage and in healthy controls (n= 18). We found a significant reduction in overall SCRs, arousal ratings and valence extremity scores in right-lesioned patients, as compared to left-lesioned patients and healthy controls. Additional analyses of correlations between subjective arousal ratings resp. SCR and normative arousal ratings revealed that both lesion groups had evaluative and physiological difficulties to discover changes in stimulus arousal. Although no group differences emerged on overall ratings of valence, analysis of correlations between subjective and normative valence ratings displayed markedly reduced accuracy in right-lesioned patients, as compared to left-lesioned patients and healthy controls. Our findings support the hypothesis that the left and right insulae subserve different functions in emotion processing, potentially due to asymmetrical representations of autonomic information in the left and right human forebrain. The right insula may serve as integral node for sympathetic arousal and cognitive affective processing.
Development of an integrated structural biology platform specialized for sub-100 kDa protein complexes to support biologics discovery and rational engineering
Authors: Iozzo Yuri , Qiu Yu , Xu Albert , Park Anna , Wendt Maria , Zhou Yanfeng 
Published: March 2021

AbstractDeveloping a biologic medicine requires successful decision making at each step of selection, optimization, and/or combination of the right candidates at early research stages. Knowing the structural information and binding pattern between drug target and discovery candidates greatly increases the possibility of success. With the cryo-EM resolution revolution and rapid development of computational software, we have evaluated and integrated different tools in structural biology and the computation field and established a highly cost-effective platform, which allows us to obtain fast and accurate structural information for biologics projects with a close to 100% success rate and as fast as weeks turn-around time. Here we report four case studies selected from over 40 different protein structures and share how we integrate cryo-EM structure determination, computational structure modeling, and molecular dynamics simulation. With proper decision making and strategic planning, the platform allows us to obtain quality results within days to weeks, including sub-100 kDa complexes which are usually considered as a challenge due to their small size. Our utilization of this differential approach and use of multiple software packages, allows to manage priorities and resources to achieve goals quickly and efficiently. We demonstrate how to effectively overcome particle orientation bias by altering complex composition. In several of our examples, we use glycan density to facilitate interpretation of low-resolution 3D reconstruction and epitope mapping. Protein information plays an important role in our cryo-EM projects, especially in cases where we see significant challenges in obtaining high-resolution 3D maps.
Dioxin-elicited decrease in cobalamin redirects hepatic propionyl-CoA metabolism to the β–oxidation-like pathway resulting in acrylyl-CoA conjugate accumulation
Authors: Orlowska Karina , Fling Russ R. , Nault Rance , Sink Warren J. , Schilmiller Anthony L. , Zacharewski Tim 
Published: March 2021

ABSTRACT2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which induces diverse biological and toxic effects, including the reprograming of intermediate metabolism, mediated by the aryl hydrocarbon receptor (AHR). Targeted LC-MS analysis of hepatic extracts from mice gavaged with TCDD every 4 days for 28 days detected an increase in S-(2-carboxyethyl)-L-cysteine, a conjugate produced following the spontaneous reaction between the sulfhydryl group of cysteine and highly reactive acrylyl-CoA, an intermediate in the cobalamin (Cbl)-independent β–oxidation-like metabolism of propionyl-CoA. In addition to repressing genes in both the canonical Cbl-dependent carboxylase and the alternate Cbl-independent β–oxidation-like pathways at 30 μg/kg TCDD, methylmalonyl-CoA mutase (MUT) activity was inhibited at lower doses. Moreover, TCDD decreased serum Cbl levels and hepatic cobalt levels while eliciting negligible effects on gene expression associated with Cbl absorption, transport, trafficking, or the derivatization to 5’-deoxy-adenosylcobalamin (AdoCbl), the required MUT cofactor. In addition to inducingAcod1that encodes for aconitate decarboxylase 1, the enzyme responsible for the decarboxylation cis-aconitate to itaconate, TCDD also dose-dependently increased itaconate levels in hepatic extracts. MUT inhibition is consistent with itaconate activation to itaconyl-CoA, a MUT suicide inactivator that adducts AdoCbl, that in turn, inhibits MUT activity and reduces Cbl levels. Collectively, these results suggest the decrease in MUT activity is due to Cbl depletion following TCDD treatment that redirected propionyl-CoA metabolism to the alternate Cbl-independent β–oxidation-like pathway. The resulting hepatic accumulation of acrylyl-CoA likely contributes to TCDD-elicited hepatotoxicity and the multi-hit progression of steatosis to steatohepatitis with fibrosis.
PyDamage: automated ancient damage identification and estimation for contigs in ancient DNAde novoassembly
Authors: Borry Maxime , Hübner Alexander , Rohrlach A.B. , Warinner Christina 
Published: March 2021

ABSTRACTDNAde novoassembly can be used to reconstruct longer stretches of DNA (contigs), including genes and even genomes, from short DNA sequencing reads. Applying this technique to metagenomic data derived from archaeological remains, such as paleofeces and dental calculus, we can investigate past microbiome functional diversity that may be absent or underrepresented in the modern microbiome gene catalogue. However, compared to modern samples, ancient samples are often burdened with environmental contamination, resulting in metagenomic datasets that represent mixtures of ancient and modern DNA. The ability to rapidly and reliably establish the authenticity and integrity of ancient samples is essential for ancient DNA studies, and the ability to distinguish between ancient and modern sequences is particularly important for ancient microbiome studies. Characteristic patterns of ancient DNA damage, namely DNA fragmentation and cytosine deamination (observed as C-to-T transitions) are typically used to authenticate ancient samples and sequences. However, existing tools for inspecting and filtering aDNA damage either compute it at the read level, which leads to high data loss and lower quality when used in combination with de novo assembly, or require manual inspection, which is impractical for ancient assemblies that typically contain tens to hundreds of thousands of contigs. To address these challenges, we designed PyDamage, a robust, automated approach for aDNA damage estimation and authentication ofde novoassembled aDNA. PyDamage uses a likelihood ratio based approach to discriminate between truly ancient contigs and contigs originating from modern contamination. We test PyDamage on both simulated, and empirical aDNA data from archaeological paleofeces, and we demonstrate its ability to reliably and automatically identify contigs bearing DNA damage characteristic of aDNA. Coupled with aDNAde novoassembly, PyDamage opens up new doors to explore functional diversity in ancient metagenomic datasets.
The Hippo pathway transcriptional co-activator YAP is involved in head regeneration and bud development inHydra
Authors: Unni Manu , Reddy Puli Chandramouli , Galande Sanjeev 
Published: March 2021

AbstractThe Hippo signaling pathway has been shown to be involved in the regulation of cellular identity, cell/tissue size maintenance and mechanotransduction. The Hippo pathway consists of a kinase cascade which determines the nucleo-cytoplasmic localization of YAP in the cell. YAP is the effector protein in the Hippo pathway which acts as a transcriptional cofactor for TEAD. Phosphorylation of YAP upon activation of the Hippo pathway prevents it from entering the nucleus and hence abrogates its function in transcription of target genes. In Cnidaria, the information on the regulatory roles of the Hippo pathway is virtually lacking. Here, we report for the first time the existence of a complete set of Hippo pathway core components inHydra. By studying their phylogeny and domain organization, we report evolutionary conservation of the components of the Hippo pathway. Protein modelling suggested conservation of YAP-TEAD interaction inHydra. We also characterized the expression pattern of the homologs ofyap, hippo, mobandsavinHydrausing whole mount RNA in situ hybridization and report their possible role in stem cell maintenance. Immunofluorescence assay revealed thatHvul_YAP expressing cells occur in clusters in the body column and are excluded in the terminally differentiated regions. The YAP expressing cells are recruited early during head regeneration and budding implicating the Hippo pathway in early response to injury or establishment of oral fate. These cells exhibit a non-clustered existence at the site of regeneration and budding, indicating the involvement of a new population of YAP expressing cells during oral fate specification. Collectively, we posit that the Hippo pathway is an important signaling system inHydra, its components are ubiquitously expressed in theHydrabody column, and may play crucial role inHydraoral fate specification.
Weak effect ofGypsyretrotransposon bursts onSonneratia albasalt stress gene expression
Authors: Wang Yushuai , Dai Aimei , Tang Tian 
Published: March 2021

AbstractBackground and AimsTransposable elements (TEs) are an important source of genetic diversity and can be co-opted for the regulation of host genes. However, to what extent the pervasive TE colonization of plant genomes has contributed to stress adaptation remains controversial. Plants inhabiting harsh environments in nature provide a unique opportunity to answer this question.MethodsWe compared TE compositions and their evolutionary dynamics in the genomes of two mangrove species: the pioneerSonneratia albaand its less salt-tolerant relativeS. caseolaris. Age distribution, strength of purifying selection and the removal rate of LTR (long terminal repeat) retrotransposons were estimated. Phylogenetic analysis of LTR retrotransposons and their distribution in the genome ofS. albawere surveyed. Small RNA sequencing and whole-genome bisulfite sequencing was conducted using leaves ofS. alba. Expression pattern of LTR retrotransposons and their nearby genes were examined using RNA-seq data ofS. albaunder different salt treatments.Key ResultsS. albapossesses more TEs thanS. caseolaris. Particularly, many more youngGypsyLTR retrotransposons have accumulated inS. albathan inS. caseolarisdespite an increase in purifying selection against TE insertions. The top two most abundantGypsyfamilies inS. albapreferentially insert in gene-poor regions. They are under relaxed epigenetic repression, probably due to the presence of CHROMO domains in their 3’-ends. Although a considerable number of TEs inS. albashowed differential expression under salt stress, only four copies were significantly correlated with their nearby genes in expression levels. One such TE-gene pair involvesAbscisic acid 8’-hydroxylase 3functioning in abscisic acid catabolism.ConclusionsThis study sheds light on the evolutionary dynamics and potential function of TEs in an extremophile. Our results suggest that the conclusion on co-option of TEs should be cautious even though activation of TEs by stress might be prevalent.
Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike protein and the human ACE2 receptor
Authors: Chen Chen , Boorla Veda Sheersh , Banerjee Deepro , Chowdhury Ratul , Cavener Victoria S , Nissly Ruth H , Gontu Abhinay , Boyle Nina R , Vandergrift Kurt , Nair Meera Surendran , Kuchipudi Suresh V , Maranas Costas D. 
Published: March 2021

ABSTRACTThe association of the receptor binding domain (RBD) of SARS-CoV-2 viral spike with human angiotensin converting enzyme (hACE2) represents the first required step for viral entry. Amino acid changes in the RBD have been implicated with increased infectivity and potential for immune evasion. Reliably predicting the effect of amino acid changes in the ability of the RBD to interact more strongly with the hACE2 receptor can help assess the public health implications and the potential for spillover and adaptation into other animals. Here, we introduce a two-step framework that first relies on 48 independent 4-ns molecular dynamics (MD) trajectories of RBD-hACE2 variants to collect binding energy terms decomposed into Coulombic, covalent, van der Waals, lipophilic, generalized Born electrostatic solvation, hydrogen-bonding, π-π packing and self-contact correction terms. The second step implements a neural network to classify and quantitatively predict binding affinity using the decomposed energy terms as descriptors. The computational base achieves an accuracy of 82.2% in terms of correctly classifying single amino-acid substitution variants of the RBD as worsening or improving binding affinity for hACE2 and a correlation coefficient r of 0.69 between predicted and experimentally calculated binding affinities. Both metrics are calculated using a 5-fold cross validation test. Our method thus sets up a framework for effectively screening binding affinity change with unknown single and multiple amino-acid changes. This can be a very valuable tool to predict host adaptation and zoonotic spillover of current and future SARS-CoV-2 variants.
Neurogenesis mediated plasticity is associated with reduced neuronal activity in CA1 during context fear memory retrieval
Authors: Evans Alexandria , Terstege Dylan J. , Scott Gavin A. , Tsutsui Mio , Epp Jonathan R. 
Published: March 2021

AbstractAdult hippocampal neurogenesis has been demonstrated to affect learning and memory in numerous ways. Several studies have now demonstrated that increased neurogenesis can induce forgetting of memories acquired prior to the manipulation of neurogenesis and, as a result of this forgetting can also facilitate new learning. However, the mechanisms mediating neurogenesis-induced forgetting are not well understood. Here, we used a subregion-based analysis of the immediate early gene c-Fos as well as in vivo fiber photometry to determine changes in activity corresponding with neurogenesis induced forgetting. We found that increasing neurogenesis led to reduced CA1 activity during context memory retrieval. We also demonstrate here that perineuronal net expression in areas CA1 is bidirectionally altered by the levels or activity of adult generated neurons in the dentate gyrus. These results suggest that neurogenesis may induce forgetting by disrupting perineuronal nets in CA1 which may otherwise protect memories from degradation.