bluuebunny/crossref_metadata_2025_split huggingface dataset:
Which policies most effectively reduce SARS-CoV-2 transmission in schools?
Authors: Bershteyn Anna , Kim Hae-Young , McGillen Jessica , Braithwaite R. Scott 
Published: November 2020

AbstractIntroductionNew York City (NYC) has the largest public school system in the United States (US). During the SARS-CoV-2 pandemic, NYC was the first major US city to open schools for in-person learning in the 2020-2021 academic year. Several policies were implemented to reduce the risk of in-school transmission, including infection control measures (facemasks, physical distancing, enhanced indoor ventilation, cohorting of small groups, and hand hygiene), option of all-remote instruction, alternative options for how class schedules would rotate in-person and remote instruction, daily symptom screening, and testing 10-20% of students and staff weekly or monthly depending on local case rates. We sought to determine which of these policies had the greatest impact on reducing the risk of in-school transmission.MethodsWe evaluated the impact of each policy by referring to global benchmarks for the secondary attack rate (SAR) of SARS-CoV-2 in school settings and by simulating the potential for transmission in NYC’s rotating cohort schedules, in which teachers could act as “bridges” across rotating cohorts. We estimated the impact of (1) infection control measures, (2) providing an option of all-remote instruction, (3) choice of class scheduling for in-person learners, (4) daily symptom screening, (5) testing to curtail transmission, and (6) testing to identify school outbreaks. Each policy was assessed independently of other policies, with the exception of symptom screening and random testing, which were assessed both independently and jointly.ResultsAmong the policies analyzed, the greatest transmission reduction was associated with the infection control measures, followed by small class cohorts with an option for all-remote instruction, symptom screening, and finally randomly testing 10-20% of school attendees. Assuming adult staff are the primary source of within-school SARS-CoV-2 transmission, weekly testing of staff could be at least as effective as symptom screening, and potentially more so if testing days occur in the beginning of the workweek with results available by the following day. A combination of daily symptom screening and testing on the first workday of each week could reduce transmission by 70%.ConclusionsAdherence to infection control is the highest priority for safe school re-opening. Further transmission reduction can be achieved through small rotating class cohorts with an option for remote learning, widespread testing at the beginning of the work week, and daily symptom screening and self-isolation. Randomly testing 10-20% of attendees weekly or monthly does not meaningfully curtail transmission and may not detect outbreaks before they have spread beyond a handful of individuals. School systems considering re-opening during the SARS-CoV-2 pandemic or similarly virulent respiratory disease outbreaks should consider these relative impacts when setting policy priorities.
Robotic Search for Optimal Cell Culture in Regenerative Medicine
Authors: Kanda Genki N. , Tsuzuki Taku , Terada Motoki , Sakai Noriko , Motozawa Naohiro , Masuda Tomohiro , Nishida Mitsuhiro , Watanabe Chihaya T. , Higashi Tatsuki , Horiguchi Shuhei A. , Kudo Taku , Kamei Motohisa , Sunagawa Genshiro A. , Matsukuma Kenji , Sakurada Takeshi , Ozawa Yosuke , Takahashi Masayo , Takahashi Koichi , Natsume Tohru 
Published: November 2020

ABSTRACTInduced differentiation is one of the most experience- and skill-dependent experimental processes in regenerative medicine, and establishing optimal conditions often takes years. We developed a robotic AI system with a batch Bayesian optimization algorithm that autonomously induces the differentiation of induced pluripotent stem cell-derived retinal pigment epithelial (iPSC-RPE) cells. The system performed 216 forty-day cell culture experiments, with a total experimentation time of 8,640 days. From 200 million possible parameter combinations, the system performed cell culture in 143 different conditions in 111 days, resulting in 88% better iPSC-RPE production than that by the pre-optimized culture in terms of pigmented scores. Our work demonstrates that the use of autonomous robotic AI systems drastically accelerates systematic and unbiased exploration of experimental search space, suggesting immense use in medicine and research.
Dynamic regulation of anterior-posterior patterning genes in livingDrosophilaembryos
Authors: Fukaya Takashi 
Published: November 2020

SummaryExpression of the gap and pair-rule genes plays an essential role in body segmentation duringDrosophilaembryogenesis [1–5]. However, it remains unclear how precise expression patterns of these key developmental genes arise from stochastic transcriptional activation at the single cell level. Here, I employed genome editing and live imaging approaches to comprehensively visualize regulation of the gap and pair-rule genes at the endogenous loci. Quantitative image analysis revealed that the total duration of active transcription (transcription period) is a major determinant of spatial patterning of gene expression in early embryos. The length of transcription period is regulated by the continuity of bursting activities in individual nuclei, with core expression domain producing more bursts than boundary region. Each gene exhibits distinct rate of nascent RNA production during transcriptional bursting, which contributes to gene-to-gene variability in the total output. I also provide evidence for “enhancer competition”, wherein a distal weak enhancer interferes with transcriptional activation by a strong proximal enhancer to downregulate the length of transcription period without changing the transcription rate. Analysis of endogenoushunchback(hb) locus revealed that the removal of distal shadow enhancer induces strong ectopic transcriptional activation, which suppresses refinement of broad expression domain into narrower stripe pattern at the anterior part of embryos. This study provides key insights into the link between transcriptional bursting, enhancer-promoter interaction and spatiotemporal patterning of gene expression during animal development.
O-GlcNAcAtlas: A Database of Experimentally Identified O-GlcNAc Sites and Proteins
Authors: Ma Junfeng , Li Yaoxiang , Hou Chunyan , Wu Ci 
Published: November 2020

ABSTRACTO-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification (i.e., O-GlcNAcylation) on serine/threonine residues of proteins. As a unique intracellular monosaccharide modification, protein O-GlcNAcylation plays important roles in almost all biochemical processes examined. Aberrant O-GlcNAcylation underlies the etiologies of a number of chronic diseases (including cancer, diabetes, and neurodegenerative disease). With the tremendous improvement of techniques, thousands of proteins along with their O-GlcNAc sites have been reported. However, until now there is no database dedicated to accommodate the rapid accumulation of such information. Thus, O-GlcNAcAtlas is created to integrate all experimentally identified O-GlcNAc sites and proteins from 1984 to Dec, 2019. O-GlcNAcAtlas consists of two datasets (Dataset-I and Dataset-II, for unambiguously identified sites and ambiguously identified sites, respectively), representing a total number of 4571 O-GlcNAc modified proteins. For each protein, comprehensive information (including gene name, organism, modification sites, site mapping methods and literature references) is provided. To solve the heterogeneity among the data collected from different sources, the sequence identity of these reported O-GlcNAc peptides are mapped to the UniProtKB protein entries. To our knowledge, O-GlcNAcAtlas is the comprehensive and curated database encapsulating all O-GlcNAc sites and proteins identified in the past 35 years. We expect that O-GlcNAcAtlas will be a useful resource which will facilitate site-specific O-GlcNAc functional studies and computational analyses of protein O-GlcNAcylation. The public version of the web interface to the O-GlcNAcAtlas can be found athttps://oglcnac.org.
The pluripotent stem cell-specific transcript ESRG is dispensable for human pluripotency
Authors: Takahashi Kazutoshi , Nakamura Michiko , Narita Megumi , Watanabe Akira , Ueda Mai , Takashima Yasuhiro , Yamanaka Shinya 
Published: November 2020

AbstractHuman pluripotent stem cells (PSCs) express human endogenous retrovirus type-H (HERV-H), which exists as more than a thousand copies on the human genome and frequently produces chimeric transcripts as long-non-coding RNAs (lncRNAs) fused with downstream neighbor genes. Previous studies showed that HERV-H expression is required for the maintenance of PSC identity, and aberrant HERV-H expression attenuates neural differentiation potentials, however, little is known about the actual of function of HERV-H. In this study, we focused on ESRG, which is known as a PSC-related HERV-H-driven lncRNA. The global transcriptome data of various tissues and cell lines and quantitative expression analysis of PSCs showed that ESRG expression is much higher than other HERV-Hs and tightly silenced after differentiation. However, the loss of function by the complete excision of the entire ESRG gene body using a CRISPR/Cas9 platform revealed that ESRG is dispensable for the maintenance of the primed and naïve pluripotent states. The loss of ESRG hardly affected the global gene expression of PSCs or the differentiation potential toward trilineage. Differentiated cells derived from ESRG-deficient PSCs retained the potential to be reprogrammed into induced PSCs (iPSCs) by the forced expression of OCT3/4, SOX2, and KLF4. In conclusion, ESRG is dispensable for the maintenance and recapturing of human pluripotency.
The complex history of genome duplication and hybridization in North American gray treefrogs
Authors: Booker William W. , Gerhardt H. Carl , Lemmon Alan R. , Ptacek Margaret B. , Hassinger Alyssa T. B. , Schul Johannes , Lemmon Emily Moriarty 
Published: November 2020

AbstractPolyploid speciation has played an important role in evolutionary history across the tree of life, yet there remain large gaps in our understanding of how polyploid species form and persist. While systematic studies have been conducted in numerous polyploid complexes, recent advances in sequencing technology have demonstrated that conclusions from data-limited studies may be spurious and misleading. The North American gray treefrog complex, consisting of the diploidHyla chrysoscelisand the tetraploidHyla versicolor, has long been used as a model system in a variety of biological fields, yet all taxonomic studies to date were conducted with only a few loci from nuclear and mitochondrial genomes. Here, we utilized anchored hybrid enrichment and high-throughput sequencing to capture hundreds of loci along with whole mitochondrial genomes to investigate the evolutionary history of this complex. We used several phylogenetic and population genetic methods, including coalescent simulations and testing of polyploid speciation models with Approximate Bayesian Computation (ABC), to determine that H. versicolor was most likely formed via autopolyploidization from a now extinct lineage of H. chrysoscelis. We also uncovered evidence of significant hybridization between diploids and tetraploids where they co-occur, and show that historical hybridization between these groups led to the re-formation of distinct polyploid lineages following the initial whole genome duplication event. Our study indicates that a wide variety of methods and explicit model testing of polyploid histories can greatly facilitate efforts to uncover the evolutionary history of polyploid complexes.
Detection of cross-frequency coupling between brain areas: an extension of phase-linearity measurement
Authors: Sorrentino Pierpaolo , Ambrosanio Michele , Rucco Rosaria , Cabral Joana , Gollo Leonardo L. , Breakspear Michael , Baselice Fabio 
Published: November 2020

AbstractThe current paper proposes a method to estimate phase to phase cross-frequency coupling between brain areas, applied to broadband signals, without any a priori hypothesis about the frequency of the synchronized components. N:m synchronization is the only form of cross-frequency synchronization that allows the exchange of information at the time resolution of the faster signal, hence likely to play a fundamental role in large-scale coordination of brain activity. The proposed method, named cross-frequency phase linearity measurement (CF-PLM), builds and expands upon the phase linearity measurement, an iso-frequency connectivity metrics previously published by our group. The main idea lies in using the shape of the interferometric spectrum of the two analyzed signals in order to estimate the strength of cross-frequency coupling. Here, we demonstrate that the CF-PLM successfully retrieves the (different) frequencies of the original broad-band signals involved in the connectivity process. Furthermore, if the broadband signal has some frequency components that are synchronized in iso-frequency and some others that are synchronized in cross-frequency, our methodology can successfully disentangle them and describe the behaviour of each frequency component separately. We first provide a theoretical explanation of the metrics. Then, we test the proposed metric on simulated data from coupled oscillators synchronized in iso- and cross-frequency (using both Rössler and Kuramoto oscillator models), and subsequently apply it on real data from brain activity, using source-reconstructed Magnetoencephalography (MEG) data. In the synthetic data, our results show reliable estimates even in the presence of noise and limited sample sizes. In the real signals, components synchronized in cross-frequency are retrieved, together with their oscillation frequencies. All in all, our method is useful to estimate n:m synchronization, based solely on the phase of the signals (independently of the amplitude), and no a-priori hypothesis is available about the expected frequencies. Our method can be exploited to more accurately describe patterns of cross-frequency synchronization and determine the central frequencies involved in the coupling.
Non-linear manifold learning in fMRI uncovers a low-dimensional space of brain dynamics
Authors: Gao Siyuan , Mishne Gal , Scheinost Dustin 
Published: November 2020

AbstractLarge-scale brain dynamics are believed to lie in a latent, low-dimensional space. Typically, the embeddings of brain scans are derived independently from different cognitive tasks or resting-state data, ignoring a potentially large—and shared—portion of this space. Here, we establish that a shared, robust, and interpretable low-dimensional space of brain dynamics can be recovered from a rich repertoire of task based fMRI data. This occurs when relying on non-linear approaches as opposed to traditional linear methods. The embedding maintains proper temporal progression of the tasks, revealing brain states and the dynamics of network integration. We demonstrate that resting-state data embeds fully onto the same task embedding, indicating similar brain states are present in both task and resting-state data. Our findings suggest analysis of fMRI data from multiple cognitive tasks in a low-dimensional space is possible and desirable, and our proposed framework can thus provide an interpretable framework to investigate brain dynamics in the low-dimensional space.
Eosinophil peroxidase induces inflammation in a mouse model of dermatitis
Authors: Roth-Carter Quinn R. , Luo Huijun , Ochkur Sergei I. , Jacobsen Elizabeth A. , Datena Meredith , Fryer Allison D. , Lee James J. , Jacoby David B. 
Published: November 2020

ABSTRACTEosinophils play an important role in mediating itch and inflammation in dermatitis. The role of the eosinophil granule protein eosinophil peroxidase (EPX) in mediating inflammation and itch was tested in a dermatitis mouse model. Mice were sensitized to trimellitic anhydride (TMA) and subsequently challenged chronically on the ear to establish dermatitis. Loss of EPX (in EPX (-/-) mice) or blocking EPX with the drug resorcinol significantly reduced dermatitis in mice exposed to TMA. Resorcinol also reduced levels of thymic stromal lymphopoietin protein (TSLP) in skin. Further studies showed that EPX increased different cytokines in keratinocytes in cell culture via two distinct mechanisms. EPX induced TSLP expression requires lysophosphatidic acid signaling while EPX induced expression of TNF-α, CSF2, CSF3, and IL1α required IL-1 signaling. We also showed that blocking IL-1 reduced inflammation in skin following TMA exposure in mice. Thus, EPX is an important mediator of inflammation and itch, that are mediated via at least two pathways. This suggests that both EPX and its’ signaling pathways may provide novel therapeutic strategies in dermatitis.
The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients
Authors: Pyfrom Sarah , Paneru Bam , Knoxx James J. , Cancro Michael P. , Posso Sylvia , Buckner Jane H. , Anguera Montserrat C. 
Published: November 2020

ABSTRACTSystemic lupus erythematous (SLE) is a female-predominant disease characterized by autoimmune B cells and pathogenic autoantibody production. Individuals with two or more X chromosomes are at increased risk for SLE, suggesting that X-linked genes contribute to the observed sex-bias of this disease. To normalize X-linked gene expression between sexes, one X in female cells is randomly selected for transcriptional silencing through X-Chromosome Inactivation (XCI), resulting in allele-specific enrichment of epigenetic modifications, including histone methylation and the long noncoding RNA XIST/Xist on the inactive X (Xi). As we have previously shown that epigenetic regulation of the Xi in female lymphocytes from mice is unexpectedly dynamic, we used RNA FISH and immunofluorescence to profile epigenetic features of the Xi at the single cell level in human B cell subsets from pediatric and adult SLE patients and healthy controls. Our data reveal that abnormal XCI maintenance in B cells is a feature of SLE. Using single-cell and bulk cell RNA sequencing datasets, we found that novel X-linked immunity genes escape XCI in specific healthy human B cell subsets, and that human SLE B cells exhibit aberrant expression of X-linked genes and XIST RNA Interactome genes. Our data reveal that mislocalized XIST RNA, coupled with a dramatic reduction in heterochromatic modifications at the Xi in SLE, predispose for aberrant X-linked gene expression from the Xi, thus defining a novel genetic and epigenetic pathway that affects X-linked gene expression in human SLE B cells and likely contributes to the female-bias in SLE.
Phasic inhibition of dopamine neurons is an instrumental punisher
Authors: Peng Constance Yunzhi , Jean-Richard-dit-Bressel Philip , Gilchrist Sophia , Power John M. , McNally Gavan P. 
Published: November 2020

AbstractIt is well established that the activity of VTA dopamine neurons is sufficient to serve as a Pavlovian reinforcer but whether this activity can also serve as instrumental reinforcer is less well understood. Here we studied the effects of optogenetic inhibition of VTA dopamine neurons in instrumental conditioning preparations. We show that optogenetic inhibition of VTA dopamine neurons causes a response-specific, contingency-sensitive suppression of instrumental responding. This suppression was due to instrumental response, not Pavlovian stimulus, learning and could not be attributed to deepened instrumental extinction learning. These effects of optogenetic inhibition of VTA dopamine neurons on instrumental responding are formally similar to the effects of aversive events in instrumental preparations and show that optogenetic inhibition of VTA dopamine neurons is sufficient to serve as an instrumental punisher.
Non-parametric Bayesian density estimation for biological sequence space with applications to pre-mRNA splicing and the karyotypic diversity of human cancer
Authors: Chen Wei-Chia , Zhou Juannan , Sheltzer Jason M , Kinney Justin B , McCandlish David M 
Published: November 2020

AbstractDensity estimation in sequence space is a fundamental problem in machine learning that is of great importance in computational biology. Due to the discrete nature and large dimensionality of sequence space, how best to estimate such probability distributions from a sample of observed sequences remains unclear. One common strategy for addressing this problem is to estimate the probability distribution using maximum entropy, i.e. calculating point estimates for some set of correlations based on the observed sequences and predicting the probability distribution that is as uniform as possible while still matching these point estimates. Building on recent advances in Bayesian field-theoretic density estimation, we present a generalization of this maximum entropy approach that provides greater expressivity in regions of sequence space where data is plentiful while still maintaining a conservative maximum entropy char-acter in regions of sequence space where data is sparse or absent. In particular, we define a family of priors for probability distributions over sequence space with a single hyper-parameter that controls the expected magnitude of higher-order correlations. This family of priors then results in a corresponding one-dimensional family of maximum a posteriori estimates that interpolate smoothly between the maximum entropy estimate and the observed sample frequencies. To demonstrate the power of this method, we use it to explore the high-dimensional geometry of the distribution of 5′ splice sites found in the human genome and to understand the accumulation of chromosomal abnormalities during cancer progression.
The Transcription Factor TEAD4 Enhances Lung Adenocarcinoma Malignancy through Enhancing PKM2 Mediated Glycolysis
Authors: Hu Yan , Mu Hanshuo , Deng Zhiping 
Published: November 2020

AbstractLung adenocarcinoma (LUAD) is a deadly disease with a hallmark of aberrant metabolism. The role of TEAD4 in LUAD is rarely reported as well as its potential mechanisms. The expression level of TEAD4 and PKM2 was measured by quantitative real-time PCR and western blot. Luciferase reporter assay were employed to verify the effect of TEAD4 on PKM2 promoter as well as TEAD4/PKM2 axis on reporter activity of HIF-1α. Glycolysis was investigated according to glucose consumption, lactate production and the extracellular acidification rate (ECAR). Cell Counting Kit-8 was used to assess cell viability. The present study indicated that TEAD4 and PKM2 were upregulated in LUAD and closely related to prognosis. Mechanistic investigations identified that TEAD4 played a key role as a transcription factor and promoted PKM2 transcription and expression, which further altered the reporter activity of HIF-1α and upregulated HIF-1α-targeted glycolytic genes GLUT1 and HK2. Functional assays revealed that TEAD4 and PKM2 affected glycolytic and 2-DG blocked the positive function of TEAD4 and PKM2 on glycolytic. Besides, TEAD4/PKM2 axis affects LUAD cells survival through glycolysis. Together, these data provided evidence that both TEAD4 and PKM2 were poor prognosticator. Targeting TEAD4/PKM2 axis might be an effective therapeutic strategy for LUAD.