bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amplified cortical tracking of word-level features of continuous competing speech in older adults
Authors: Mesik Juraj , Ray Lucia A. , Wojtczak Magdalena 
Published: December 2020

AbstractSpeech-in-noise comprehension difficulties are common among the elderly population, yet traditional objective measures of speech perception are largely insensitive to this deficit, particularly in the absence of clinical hearing loss. In recent years, a growing body of research in young normal-hearing adults has demonstrated that high-level features related to speech semantics and lexical predictability elicit strong centro-parietal negativity in the EEG signal around 400 ms following the word onset. Here we investigate effects of age on cortical tracking of these word-level features within a two-talker speech mixture, and their relationship with self-reported difficulties with speech-in-noise understanding. While undergoing EEG recordings, younger and older adult participants listened to a continuous narrative story in the presence of a distractor story. We then utilized forward encoding models to estimate cortical tracking of three speech features: 1) “semantic” dissimilarity of each word relative to the preceding context, 2) lexical surprisal for each word, and 3) overall word audibility. Our results revealed robust tracking of all three features for attended speech, with surprisal and word audibility showing significantly stronger contributions to neural activity than dissimilarity. Additionally, older adults exhibited significantly stronger tracking of surprisal and audibility than younger adults, especially over frontal electrode sites, potentially reflecting increased listening effort. Finally, neuro-behavioral analyses revealed trends of a negative relationship between subjective speech-in-noise perception difficulties and the model goodness-of-fit for attended speech, as well as a positive relationship between task performance and the goodness-of-fit, indicating behavioral relevance of these measures. Together, our results demonstrate the utility of modeling cortical responses to multi-talker speech using complex, word-level features and the potential for their use to study changes in speech processing due to aging and hearing loss.
Multiple overlapping dynamic patterns of the visual sensory network in schizophrenia
Authors: Sendi Mohammad S. E , Pearlson Godfrey D. , Mathalon Daniel H. , Ford Judith M. , Preda Adrian , van Erp Theo G. M. , Calhoun Vince D. 
Published: December 2020

AbstractAlthough visual processing impairments have been explored in schizophrenia (SZ), their underlying neurobiology of the visual processing impairments has not been widely studied. Also, while some research has hinted at differences in information transfer and flow in SZ, there are few investigations of the dynamics of functional connectivity within visual networks. In this study, we analyzed resting-state fMRI data of the visual sensory network (VSN) in 160 healthy control (HC) subjects and 151 SZ subjects. We estimated 9 independent components within the VSN. Then, we calculated the dynamic functional network connectivity (dFNC) using the Pearson correlation. Next, using k-means clustering, we partitioned the dFNCs into five distinct states, and then we calculated the portion of time each subject spent in each state, that we termed the occupancy rate (OCR). Using OCR, we compared HC with SZ subjects and investigated the link between OCR and visual learning in SZ subjects. Besides, we compared the VSN functional connectivity of SZ and HC subjects in each state. We found that this network is indeed highly dynamic. Each state represents a unique connectivity pattern of fluctuations in VSN FNC, and all states showed significant disruption in SZ. Overall, HC showed stronger connectivity within the VSN in states. SZ subjects spent more time in a state in which the connectivity between the middle temporal gyrus and other regions of VNS is highly negative. Besides, OCR in a state with strong positive connectivity between middle temporal gyrus and other regions correlated significantly with visual learning scores in SZ.
STING Nuclear Partners Contribute to Innate Immune Signalling Responses
Authors: Dixon Charles R. , Malik Poonam , de las Heras Jose I. , Saiz-Ros Natalia , de Lima Alves Flavia , Tingey Mark , Gaunt Eleanor , Richardson A. Christine , Kelly David A. , Goldberg Martin W. , Towers Greg J. , Yang Weidong , Rappsilber Juri , Digard Paul , Schirmer Eric C. 
Published: December 2020

AbstractSTING and cGAS initiate innate immune responses (IIR) by recognizing cytoplasmic pathogen dsDNA and activating signaling cascades from the ER; however, another less investigated pool of STING resides in the nuclear envelope. We find that STING in the inner nuclear membrane increases mobility and changes localization upon IIR activation both from dsDNA and poly(I:C) stimuli. We next identified nuclear partners of STING from isolated nuclear envelopes. These include several known nuclear membrane proteins, bromodomain and epigenetic enzymes, and RNA- or DNA-binding proteins. Strikingly, 17 of these DNA and RNA-binding STING partners are known to bind direct partners of the IRF3/7 transcription factors that are central drivers of IIR. We find that several of these STING partners —SYNCRIP, Men1, Ddx5, snRNP70, RPS27a, Aatf— can contribute to IIR activation and SYNCRIP can moreover protect against influenza A virus infection. These data suggest that the many roles identified for STING likely reflect its interactions with multiple RNA and DNA-binding proteins that also function in IIR.
The composition of northeast pacific fishes in a fish tank examined by eDNA metabarcoding
Authors: Turanov Sergei V. , Rutenko Olesia A. 
Published: December 2020

AbstractThe taxonomy of fish in the northeast Pacific area has been recently revised using molecular genetic methods, including the development of a reference library of DNA fragments for species identification. Such libraries are the basis for the development of non-invasive, high-throughput methods for monitoring biodiversity using environmental DNA (eDNA). In order to validate this approach, we used a water eDNA metabarcoding technique based on12S rRNAandCOImitochondrial fragments and assessed the composition of the twenty northeast Pacific fish species held in a fish tank at the Primorsky Aquarium (Vladivostok, Russia). Only the12Sfragment revealed data on fish-related operational taxonomic units (OTUs). Approximately 68% of the reads were classified into two species of the genusOncorhynchus, whose shredded fillet is used for feeding. According to the taxonomic identification for the rest of the reads, 8 out of 20 fish species in the tank (40%) were identified unambiguously, while two species could not be identified. Ten taxa can be considered conditionally identifiable since they might be concealed behind a conflicting taxonomic identification at the genus or family level. In this case, an improvement of the reference library would provide resolution. We detected contamination, which may be related to both intra-laboratory contaminants occurring during DNA extraction and water intake supplying the fish tank.
Multi cell line analysis of lysosomal proteomes reveals unique features and novel lysosomal proteins
Authors: Akter Fatema , Ponnaiyan Srigayatri , Kögler-Mohrbacher Bianca , Bleibaum Florian , Damme Markus , Renard Bernhard Y. , Winter Dominic 
Published: December 2020

AbstractLysosomes play a key role in the regulation of cellular metabolism and are increasingly recognized as highly active and diverse organelles which are involved in a large variety of processes. Their essential role is exemplified by the detrimental consequences of lysosomal malfunction, which can result in lysosomal storage disorders, neurodegenerative diseases, and cancer. Using lysosome enrichment and mass spectrometry, we investigated the lysosomal proteomes of six common cell lines. We provide first evidence for cell-type specific differences of lysosomes on a large scale, showing highly variable levels of distinct lysosomal proteins within one cell type, while others are highly conserved among cell lines. Using stable isotope labelling and bimodal distribution analysis, we identify high confidence lysosomal proteins for each cell line. Multi cell line correlation of these data reveals potential novel lysosomal proteins, and we confirm lysosomal localization for five candidates. All data are available via ProteomeXchange with identifier PXD020600.
Predicting COVID-19 cases with unknown homogeneous or heterogeneous resistance to infectivity
Authors: Shanmugam Ramalingam , Ledlow Gerald , Singh Karan P. 
Published: December 2020

AbstractThis article constructs a restricted infection rate inverse binomial-based approach to predict COVID-19 cases after a family gathering. The traditional inverse binomial (IB) model is unqualified to match the reality of COVID-19, because the data contradicts the model’s requirement that variance should be greater than expected value. A refined version of the IB model is a necessity to predict COVID-19 cases after family gatherings. Our refined version of an IB model is more appropriate and versatile, as it accommodates all potential data scenarios: equal, lesser, or greater variance than expected value.Application of the approach is based on a restricted infectivity rate and methodology on Fan et al.’s COVID-19 data, which exhibits two clusters of infectivity. Cluster 1 has a smaller number of primary cases and exhibits larger variance than the expected cases with a negative correlation of 28%, implying that the number of secondary cases is lesser when the number of primary cases increases and vice versa. The traditional inverse binomial (IB) model is appropriate for Cluster 1. The probability of contracting COVID-19 is estimated to be 0.13 among the primary, but is 0.75 among the secondary in Cluster 1, with a wider gap. Conversely, Cluster 2, exhibits smaller variance than the expected cases with a correlation of 79%, implying the number of primary and secondary cases increase or decrease together. Cluster 2 disqualifies the traditional IB model and demands its refined version. Probability of contracting COVID-19 is estimated to be 0.74 among the primary, but is 0.72 among the secondary in Cluster 2, with a narrower gap.The model’s ability to estimate the community’s health system memory for future policies to be developed is an asset of this approach. The current hazard level to be infected with COVID-19 among the primary and secondary groups are estimable and interpretable.Author SummaryCurrent statistical models are not able to accurately predict disease infection spread in the COVID-19 pandemic. We have applied a widely-used inverse binomial method to predict rates of infection after small gatherings, going from primary (original) cases to secondary (later) cases after family gatherings or social events, using the data from the Wuhan and Gansu provinces in China, where the virus first spread. The advantages of the proposed approach include that the model’s ability to estimate the community’s health system memory for future policies to be developed, as such policies might reduce COVID’s spread if not its control. In our approach, as demonstrated, the current hazard level of becoming infected with COVID-19 and the odds of contracting COVID-19 among the primary in comparison to the secondary groups are estimable and interpretable. We hope the proposed approach will be used in future epidemics.
Information rate in humans during visuomotor tracking
Authors: Lam Sze-Ying , Zénon Alexandre 
Published: December 2020

AbstractWhile previous studies of human information rate focused primarily on discrete forced-choice tasks, we extend the scope of the investigation to the framework of sensorimotor tracking of continuous signals. We show how considering information transfer in this context sheds new light on the problem; crucially, such an analysis requires one to consider and carefully disentangle the effects due to real-time information processing of surprising inputs (feedback component) from the contribution to performance due to prediction (feedforward component). We argue that only the former constitutes a faithful representation of the true information processing rate. We provide information-theoretic measures which separately quantify these components and show that they correspond to a decomposition of the total information shared between target and tracking signals. We employ a linear quadratic regulator model to provide evidence for the validity of the measures, as well as of the estimator of visual-motor delay (VMD) from experimental data, instrumental to compute them in practice. On experimental tracking data, we show that the contribution of prediction as computed by the feedforward measure increases with the predictability of the signal, confirming previous findings. Importantly, we further find the feedback component to be modulated by task difficulty, with higher information transmission rates observed with noisier signals. Such opposite trends between feedback and feedforward point to a tradeoff of cognitive resources/effort and performance gain.Author summaryPrevious investigations concluded that the human brain’s information processing rate remains fundamentally constant, irrespective of task demands. However, their conclusion rested in analyses of simple discrete-choice tasks. The present contribution recasts the question of human information rate within the context of visuomotor tasks, which provides a more ecologically relevant arena, albeit a more complex one. We argue that, while predictable aspects of inputs can be encoded virtually free of charge, real-time information transfer should be identified with the processing of surprises. We formalise this intuition by deriving from first principles a decomposition of the total information shared by inputs and outputs into a feedforward, predictive component and a feedback, error-correcting component. We find that the information measured by the feedback component, a proxy for the brain’s information processing rate, scales with the difficulty of the task at hand, in agreement with cost-benefit models of cognitive effort.
Recapitulating tumor microenvironment using preclinical 3D tissueoids model for accelerating cancer research and drug screening
Authors: Baru Ambica , Mazumdar Saumyabrata , Kundu Prabuddha , Sharma Swati , Das Purakayastha Biswa Pratim , Khan Sameena , Gupta Reeshu , Arora Nupur Mehrotra 
Published: December 2020

AbstractThe formation of three-dimensional spheroid tumor model using the scaffold-based platforms has been demonstrated over many years now. 3D tumor models are generated mainly in non-scalable culture systems, using synthetic and biological scaffolds. Many of these models fail to reflect the complex tumor microenvironment and do not allow long-term monitoring of tumor progression. This has resulted in inconsistent data in drug testing assays during preclinical and clinical studies. To overcome these limitations, we have developed 3D tissueoids model by using novel AXTEX-4D™ platform. Cancer 3D tissueoids demonstrated the basic features of 3D cell culture with rapid attachment, proliferation, and longevity with contiguous cytoskeleton and hypoxic core. This study also demonstrated greater drug resistance in 3D-MCF-7 tissueoids in comparison to 2D monolayer cell culture and the collagen-based 3D system. In conclusion, 3D-tissueoids are more responsive than 2D-cultured cells in simulating important tumor characteristics, anti-apoptotic features, and their resulting drug resistance.
BoskR– Testing Adequacy of Diversification Models Using Tree Shape
Authors: Schwery Orlando , O’Meara Brian C. 
Published: December 2020

AbstractThe study of diversification largely relies on model-based approaches, estimating rates of speciation and extinction from phylogenetic trees. While a plethora of different models exist – all with different features, strengths and weaknesses – there is increasing concern about the reliability of the inference we gain from them. Apart from simply finding the model with the best fit for the data, we should find ways to assess a model’s suitability to describe the data in an absolute sense. The R packageBoskRimplements a simple way of judging a model’s adequacy for a given phylogeny using metrics for tree shape, assuming that a model is inadequate for a phylogeny if it produces trees that are consistently dissimilar in shape from the tree that should be analyzed. Tree shape is assessed via metrics derived from the tree’s modified graph Laplacian spectrum, as provided byRPANDA. We exemplify the use of the method using simulated and empirical example phylogenies.BoskRwas mostly able to correctly distinguish trees simulated under clearly different models and revealed that not all models are adequate for the empirical example trees. We believe the metrics of tree shape to be an intuitive and relevant means of assessing diversification model adequacy. Furthermore, by implementing the approach in an openly available R package, we enable and encourage researchers to adopt adequacy testing into their workflow.
HIV reverse transcriptase pre-steady-state kinetic analysis of chain terminators and translocation inhibitors reveals interactions between magnesium and nucleotide 3′-OH
Authors: Dilmore Christopher R. , DeStefano Jeffrey J. 
Published: December 2020

AbstractDeoxythymidine triphosphate analogs with various 3′ sugar groups (-OH (dTTP), -H, -N3, -NH2, -F, -O-CH3, no group (2′,3′-didehydro-2′,3′-dideoxythymidine triphosphate (d4TTP)), and those retaining the 3′-OH but with 4′ additions (4′-C-methyl, 4′-C-ethyl) or sugar ring modifications (D-carba dTTP) were evaluated using pre-steady-state kinetics in low (0.5 mM) and high (6 mM) Mg2+with HIV reverse transcriptase (RT). Analogs showed diminished incorporation rates (k) compared to dTTP ranging from about 2-fold (3′-H, -N3, and d4TTP with high Mg2+) to >10-fold (3′-NH2and 3′-F with low Mg2+), while 3′-O-CH3dTTP incorporated much slower than other analogs. Illustrating the importance of interactions between Mg2+and the 3′-OH,kusing 5 μM dTTP and 0.5 mM Mg2+was only modestly slower (1.6-fold) than with 6 mM Mg2+, while analogs with 3′ alterations incorporated 2.8-5.1-fold slower in 0.5 mM Mg2+. In contrast, 4′-C-methyl and D-carb dTTP, which retain the 3′-OH, were not significantly affected by Mg2+. Consistent with these results, analogs with 3′ modifications were better inhibitors in 6 mMvs. 0.5 mM Mg2+. Equilibrium dissociation constant (Kd) andkpoldeterminations for dTTP and analogs lacking a 3′-OH indicated that low Mg2+caused a several-fold greater reduction inkpolwith the analogs but had little effect on Kd, results consistent with a role for 3′-OH/Mg2+interactions in catalysis rather than nucleotide binding. Overall, results emphasize the importance previously unreported interactions between Mg2+and the 3′-OH of the incoming nucleotide and suggest inhibitors with 3′-OH groups may have advantages in the low free Mg2+in physiological settings.
The Golgi-associated retrograde protein (GARP) complex plays an essential role in the maintenance of the Golgi glycosylation machinery
Authors: Khakurel Amrita , Kudlyk Tetyana , Bonifacino Juan S. , Lupashin Vladimir V. 
Published: December 2020

AbstractThe Golgi apparatus is a central hub for intracellular protein trafficking and glycosylation. Steady-state localization of glycosylation enzymes is achieved by a combination of mechanisms involving retention and vesicle recycling, but the machinery governing these mechanisms is poorly understood. Herein we show that the Golgi-associated retrograde protein (GARP) complex is a critical component of this machinery. Using multiple human cell lines, we show that depletion of GARP subunits is detrimental to N- and O-glycosylation, and reduces the stability of glycoproteins and Golgi enzymes. Moreover, GARP-KO cells exhibit impaired retention of glycosylation enzymes in the Golgi. Indeed, a RUSH assay shows that, in GARP-KO cells, the enzyme beta-1,4-galactosyltransferase 1 is not retained at the Golgi but instead is missorted to the endolysosomal compartment. We propose that the endosomal compartment is part of the trafficking itinerary of Golgi enzymes and that the GARP complex is essential for recycling and stabilization of the Golgi glycosylation machinery.
A novel antigenic site spanning domains I and III of the Zika virus envelope glycoprotein is the target of strongly neutralizing human monoclonal antibodies
Authors: Graham Stephen , Tu Huy A. , McElvany Benjamin D. , Graham Nancy R. , Grinyo Ariadna , Davidson Edgar , Doranz Benjamin J. , Diehl Sean A. , Silva Aravinda M. de , Markmann Alena Janda 
Published: December 2020

AbstractZika virus (ZIKV), a mosquito-transmitted flavivirus, caused a large epidemic in Latin America between 2015 and 2017. Effective ZIKV vaccines and treatments are urgently needed to prevent future epidemics and severe disease sequelae. People infected with ZIKV develop strongly neutralizing antibodies linked to viral clearance and durable protective immunity. To understand mechanisms of protective immunity and to support the development of ZIKV vaccines, here we characterize the properties of a strongly neutralizing antibody, B11F, isolated from a recovered ZIKV patient. Our results indicate that B11F targets a complex epitope on the virus that spans domains I and III of the envelope glycoprotein. While previous studies point to quaternary epitopes centered on domain II of ZIKV E glycoprotein as targets of strongly neutralizing and protective human antibodies, we uncover a new site spanning domain I and III as a target of strongly neutralizing human antibodies.ImportancePeople infected with Zika virus develop durable neutralizing antibodies that prevent repeat infections. In the current study, we characterize a ZIKV-neutralizing human monoclonal antibody isolated from a patient after recovery. Our studies establish a novel site on the viral envelope targeted by human neutralizing antibodies. Our results are relevant to understanding how antibodies block infection and for guiding the design and evaluation of candidate vaccines.
Definition of germ layer cell lineage alternative splicing programs reveals a critical role for Quaking in specifying cardiac cell fate
Authors: Fagg W. Samuel , Liu Naiyou , Braunschweig Ulrich , Pereira de Castro Karen Larissa , Chen Xiaoting , Ditmars Frederick S. , Widen Steven G. , Donohue John Paul , Modis Katalin , Russell William K. , Fair Jeffrey H. , Weirauch Matthew T. , Blencowe Benjamin J. , Garcia-Blanco Mariano A. 
Published: December 2020

ABSTRACTAlternative splicing is critical for development; however, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived definitive endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-enriched RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative splicing program and formation of myocytes. These changes arise in part through reduced expression ofBIN1splice variants linked to cardiac development. Mechanistically, we find that QKI represses inclusion of exon 7 inBIN1pre-mRNA via an exonic ACUAA motif, and this is concomitant with intron removal and cleavage from chromatin. Collectively, our results uncover alternative splicing programs associated with the three germ lineages and demonstrate an important role for QKI in the formation of cardiac mesoderm.