bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oscillatory entrainment of the Frequency Following Response in auditory cortical and subcortical structures
Authors: Coffey Emily B.J. , Arseneau-Bruneau Isabelle , Zhang Xiaochen , Baillet Sylvain , Zatorre Robert J. 
Published: September 2020

AbstractThere is much debate about the existence and function of neural oscillatory entrainment mechanisms in the auditory system. The frequency-following response (FFR) is an index of neural periodicity encoding that can provide a vehicle to study entrainment in frequency ranges relevant to speech and music processing. Criteria for entrainment include the presence of post-stimulus oscillations and phase alignment between stimulus and endogenous activity. To test the hypothesis of entrainment, in experiment 1 we collected FFR data to a repeated syllable using magneto- (MEG) and electroencephalography in 20 healthy adults. We observed significant oscillatory activity after stimulus offset in auditory cortex and subcortical auditory nuclei, consistent with entrainment. In these structures the FFR fundamental frequency converged from a lower value over 100 ms to the stimulus frequency, consistent with phase alignment, and diverged to a lower value after offset, consistent with relaxation to a preferred frequency. In experiment 2, we tested how transitions between stimulus frequencies affected the MEG-FFR to a train of pure-tone pairs in 30 adults. We found that the FFR was affected by the frequency of the preceding tone for up to 40 ms at subcortical levels, and even longer durations at cortical levels. Our results suggest that oscillatory entrainment may be an integral part of periodic sound representation throughout the auditory neuraxis. The functional role of this mechanism is unknown, but it could serve as a fine-scale temporal predictor for frequency information, enhancing stability and reducing susceptibility to degradation that could be useful in real-life noisy environments.
Elucidating Human Milk Oligosaccharide biosynthetic genes through network-based multiomics integration
Authors: Kellman Benjamin P. , Richelle Anne , Yang Jeong-Yeh , Chapla Digantkumar , Chiang Austin W. T. , Najera Julia , Bao Bokan , Koga Natalia , Mohammad Mahmoud A. , Bruntse Anders Bech , Haymond Morey W. , Moremen Kelley W. , Bode Lars , Lewis Nathan E. 
Published: September 2020

AbstractHuman Milk Oligosaccharides (HMOs) are abundant carbohydrates fundamental to infant health and development. Although these oligosaccharides were discovered more than half a century ago, their biosynthesis in the mammary gland remains largely uncharacterized. Here, we used a systems biology framework that integrated glycan and RNA expression data to construct an HMO biosynthetic network and predict glycosyltransferases involved. To accomplish this, we constructed models describing the most likely pathways for the synthesis of the oligosaccharides accounting for >95% of the HMO content in human milk. Through our models, we propose candidate genes for elongation, branching, fucosylation, and sialylation of HMOs. We further explored selected enzyme activities through kinetic assay and their co-regulation through transcription factor analysis. These results provide the molecular basis of HMO biosynthesis necessary to guide progress in HMO research and application with the ultimate goal of understanding and improving infant health and development.Significance statementWith the HMO biosynthesis network resolved, we can begin to connect genotypes with milk types and thereby connect clinical infant, child and even adult outcomes to specific HMOs and HMO modifications. Knowledge of these pathways can simplify the work of synthetic reproduction of these HMOs providing a roadmap for improving infant, child, and overall human health with the specific application of a newly limitless source of nutraceuticals for infants and people of all ages.
Accurate spliced alignment of long RNA sequencing reads
Authors: Sahlin Kristoffer , Mäkinen Veli 
Published: September 2020

AbstractLong-read RNA sequencing techniques are establishing themselves as the primary sequencing technique to study the transcriptome landscape. Many such analyses are dependent on read alignments. However, the error rate and sequencing length of long-read technologies create new challenges for accurately aligning these reads. We present an alignment method uLTRA based on a novel two-pass collinear chaining algorithm. Furthermore, uLTRA can be used both as a stand-alone aligner and as a wrapper around minimap2 for improved alignments in gene regions. We show that uLTRA produces higher accuracy over state-of-the-art aligners with substantially higher accuracy for small exons on simulated and synthetic data. On biological data where true read location is unknown, we show several examples where uLTRA aligns to known and novel isoforms with exon structures that are not detected with other aligners. uLTRA is available athttps://github.com/ksahlin/ultra.
Comment on “Rapid and efficientin vivoastrocyte-to-neuron conversion with regional identity and connectivity?”
Authors: Chen Gong , Li Wen , Xiang Zongqin , Xu Liang , Liu Minhui , Wang Qingsong , Lei Wenliang 
Published: September 2020

ABSTRACTRegenerating functional new neurons in the adult mammalian central nervous system (CNS) has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss. In contrast, glial cells in the CNS can divide and repopulate themselves under injury or disease conditions. Therefore, many groups around the world have been able to utilize internal glial cells to directly convert them into neurons for neural repair. We have previously demonstrated that ectopic expression of NeuroD1 in dividing glial cells can directly convert reactive glial cells into neurons. However, Wang et al. recently posted an article in bioRxiv challenging the entire field ofin vivoglia-to-neuron conversion after using one single highly toxic dose of AAV (2×1013gc/ml, 1 μl) in the mouse cortex, producing artifacts that are very difficult to interpret. We present data here that reducing AAV dosage to safe level will avoid artifacts caused by toxic dosage. We also demonstrate with Aldh1l1-CreERT2and Ai14 reporter mice that lineage-traced astrocytes can be successfully converted into NeuN+neurons after infected by AAV5 GFAP::NeuroD1. Retroviral expression of NeuroD1 further confirms our previous findings that dividing glial cells can be converted into neurons. Together, the incidence of Wang et al. sends an alarming signal to the entirein vivoreprogramming field that the dosage of viral vectors is a critical factor to consider when designing proper experiments. For AAV, we recommend a relatively safe dose of 1×1010- 1×1012gc/ml (~1 μl) in the rodent brain for cell conversion experiments addressing basic science questions. For therapeutic purpose under injury or diseased conditions, AAV dosage needs to be adjusted through a series of dose finding experiments. Moreover, we recommend that the AAV results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.
No evidence for entrainment: endogenous gamma oscillations and rhythmic flicker responses coexist in visual cortex
Authors: Duecker Katharina , Gutteling Tjerk P. , Herrmann Christoph S. , Jensen Ole 
Published: September 2020

AbstractOver the past decades, a plethora of studies have linked cortical gamma oscillations (∼30-100 Hz) to neuro-computational mechanisms. Their functional relevance, however, is still passionately debated. Here, we asked if endogenous gamma oscillations in the human brain can be entrained by a rhythmic photic drive>50 Hz. A noninvasive modulation of endogenous brain rhythms allows conclusions about their causal involvement in neurocognition. To this end, we systematically investigated oscillatory responses to a rapid sinusoidal flicker in the absence and presence of endogenous gamma oscillations using magnetoencephalography (MEG) in combination with a high-frequency projector. The photic drive produced a robust response over visual cortex to stimulation frequencies of up to 80 Hz. Strong, endogenous gamma oscillations were induced using moving grating stimuli as repeatedly done in previous research. When superimposing the flicker and the gratings, there was no evidence for phase or frequency entrainment of the endogenous gamma oscillations by the photic drive. Unexpectedly, we did not observe an amplification of the flicker response around participants’ individual gamma frequencies; rather, the magnitude of the response decreased monotonically with increasing frequency. Source reconstruction suggests that the flicker response and the gamma oscillations were produced by separate, coexistent generators in visual cortex. The presented findings challenge the notion that cortical gamma oscillations can be entrained by rhythmic visual stimulation. Instead, the mechanism generating endogenous gamma oscillations seems to be resilient to external perturbation.Significance StatementWe aimed to investigate to what extent ongoing, high-frequency oscillations in the gamma band (30-100 Hz) in the human brain can be entrained by a visual flicker. Gamma oscillations have long been suggested to coordinate neuronal firing and enable inter-regional communication. Our results demonstrate that rhythmic visual stimulation cannot hijack the dynamics of ongoing gamma oscillations; rather, the flicker response and the endogenous gamma oscillations coexist in different visual areas. Therefore, while a visual flicker evokes a strong neuronal response even at high frequencies in the gamma-band, it does not entrain endogenous gamma oscillations in visual cortex. This has important implications for interpreting studies investigating the causal and neuroprotective effects of rhythmic sensory stimulation in the gamma band.
Community-curated and standardised metadata of published ancient metagenomic samples with AncientMetagenomeDir
Authors: Fellows Yates James A. , Valtueña Aida Andrades , Vågene Ashild J. , Cribdon Becky , Velsko Irina M. , Borry Maxime , Bravo-López Miriam J. , Fernandez-Guerra Antonio , Green Eleanor J. , Ramachandran Shreya L. , Heintzman Peter D. , Spyrou Maria A. , Hübner Alexander , Gancz Abigail S. , Hider Jessica , Allshouse Aurora F. , Warinner Christina 
Published: September 2020

ABSTRACTAncient DNA and RNA are valuable data sources for a wide range of disciplines. Within the field of ancient metagenomics, the number of published genetic datasets has risen dramatically in recent years, and tracking this data for reuse is particularly important for large-scale ecological and evolutionary studies of individual microbial taxa, microbial communities, and metagenomic assemblages. AncientMetagenomeDir (archived athttps://doi.org/10.5281/zenodo.3980833) is a collection of indices of published genetic data deriving from ancient microbial samples that provides basic, standardised metadata and accession numbers to allow rapid data retrieval from online repositories. These collections are community-curated and span multiple sub-disciplines in order to ensure adequate breadth and consensus in metadata definitions, as well as longevity of the database. Internal guidelines and automated checks to facilitate compatibility with established sequence-read archives and term-ontologies ensure consistency and interoperability for future meta-analyses. This collection will also assist in standardising metadata reporting for future ancient metagenomic studies.
Alternate models of acute dyslipidemia reveal divergent pathways upon atherosclerosis initiation
Authors: Hellberg Sanna , Shavva Vladimir S. , Metso Jari , Chen Guangchun , Li Quan-Zhen , Manfè Valentina , Olofsson Peder S. , Jauhiainen Matti , Binder Christoph J. , Malin Stephen G. 
Published: September 2020

AbstractAtherosclerosis is thought to be initiated by the sub-intimal retention of apolipoprotein-B containing lipoproteins within susceptible sites of the vasculature. Understanding this initiation is not possible with current legacy mouse models of atherosclerosis. We created two mouse strains of inducible hypercholesterolemia based on conditional loss of apolipoprotein E or through inducible expression of a gain-of-function proprotein convertase subtilisin/kexin type 9 D374Y mutation. Both strains rapidly broke plasma-lipid homeostasis and converted to a state of atherogenic dyslipidemia, resulting in overt aortic-accumulation of lipoproteins within 10 days. RNA-sequencing revealed that the vascular response is completely dependent on the route taken to dyslipidemia, which nevertheless implicates known pathogenic pathways in the aetiology of atherosclerosis, and further implicates APOE as an inhibitor of inflammation. As atherosclerosis develops, a convergence of common mechanistic processes emerge in both strains with significant involvement of the immune system, and targeting of CD8 T cells can regulate a conserved aortic response. Our results define atherosclerosis initiation as highly heterogeneous process and identify multiple potential therapeutic targets that may influence disease onset.
White matter integrity requires continuous myelin synthesis at the inner tongue
Authors: Meschkat Martin , Steyer Anna M. , Weil Marie-Theres , Kusch Kathrin , Jahn Olaf , Piepkorn Lars , Agüi-Gonzalez Paola , Ngoc Phan Nhu Thi , Ruhwedel Torben , Sadowski Boguslawa , Rizzoli Silvio O. , Werner Hauke B. , Ehrenreich Hannelore , Nave Klaus-Armin , Möbius Wiebke 
Published: September 2020

SummaryMyelin, the electrically insulating axonal sheath, is composed of lipids and proteins with exceptionally long lifetime. This raises the question how myelin function is affected by myelin turnover. We have studied the integrity of myelinated tracts after experimentally preventing the formation of new myelin in the CNS of adult mice, using an inducibleMbpnull allele. Oligodendrocytes survived recombination, continued expressing myelin genes, but failed to maintain compacted myelin sheaths. Using 3D electron microscopy and mass spectrometry imaging we visualized myelin-like membranes that failed to incorporate adaxonally, most prominently at juxta-paranodes. Myelinoid body formation indicated degradation of existing myelin at the abaxonal side and at the inner tongue of the sheath. Compacted myelin thinning and shortening of internodes, with about 50% myelin lost after 20 weeks (=5 months), ultimately led to axonal pathology and neurological disease. These data reveal that functional axon-myelin units require the continuous incorporation of new myelin membranes.
A genome-scale metabolic network model and machine learning predict amino acid concentrations in Chinese Hamster Ovary cell cultures
Authors: Schinn Song-Min , Morrison Carly , Wei Wei , Zhang Lin , Lewis Nathan E. 
Published: September 2020

AbstractThe control of nutrient availability is critical to large-scale manufacturing of biotherapeutics. However, the quantification of proteinogenic amino acids is time-consuming and thus is difficult to implement for real-timein situbioprocess control. Genome-scale metabolic models describe the metabolic conversion from media nutrients to proliferation and recombinant protein production, and therefore are a promising platform forin silicomonitoring and prediction of amino acid concentrations. This potential has not been realized due to unresolved challenges: (1) the models assume an optimal and highly efficient metabolism, and therefore tend to underestimate amino acid consumption, and (2) the models assume a steady state, and therefore have a short forecast range. We address these challenges by integrating machine learning with the metabolic models. Through this we demonstrate accurate and time-course dependent prediction of individual amino acid concentration in culture medium throughout the production process. Thus, these models can be deployed to control nutrient feeding to avoid premature nutrient depletion or provide early predictions of failed bioreactor runs.
Single-cell profiling of histone modifications in the mouse brain
Authors: Bartosovic Marek , Kabbe Mukund , Castelo-Branco Gonçalo 
Published: September 2020

AbstractThe development of the mouse central nervous system (CNS) involves coordinated execution of transcriptional and epigenetic programs. These programs have been extensively studied through single-cell technologies in a pursuit to characterize the underlying cell heterogeneity. However, histone modifications pose additional layers of both positive and negative regulation that defines cellular identity. Here we show that the Cut&Tag technology can be coupled with a droplet-based single cell library preparation platform to produce high quality chromatin modifications data at a single cell resolution in tens of thousands of cells. We apply single-cell Cut&Tag (scC&T) to probe histone modifications characteristic of active promoters (H3K4me3), active promoters and enhancers (H3K27ac), active gene bodies (H3K36me3) and inactive regions (H3K27me3) and generate scC&T profiles for almost 50,000 cells. scC&T profiles of each of these histone modifications were sufficient to determine cell identity and deconvolute at single cell level regulatory principles such as promoter bivalency, spreading of H3K4me3 and promoter-enhancer connectivity. Moreover, we used scC&T to investigate the single-cell chromatin occupancy of transcription factor Olig2 and the cohesin complex component Rad21. Our results indicate that analysis of histone modifications and transcription factor occupancy at a single cell resolution can provide unique insights of epigenomic landscapes in the CNS. We also provide an online resource that can be used to interactively explore the data athttps://castelobranco.shinyapps.io/BrainCutAndTag2020/.
Intracellular stiffening competes with cortical softening in glioblastoma cells
Authors: Alibert Charlotte , Pereira David , Lardier Nathan , Etienne-Manneville Sandrine , Goud Bruno , Asnacios Atef , Manneville Jean-Baptiste 
Published: September 2020

AbstractCancer cell softening increases with the progression of the disease, suggesting that mechanical phenotyping could be used as a diagnostic or prognostic method. Here we investigate the cell mechanics of gliomas, brain tumors that originate from glial cells or glial progenitors. We use two microrheology techniques, a single cell parallel plates rheometer to probe whole cell mechanics and optical-tweezers to probe intracellular rheology. We show that cell mechanics discriminates human glioma cells of different grades. When probed globally, grade IV glioblastoma cells are softer than grade III astrocytoma cells, while they are surprisingly stiffer at the intracellular level. We explain this difference between global and local intracellular behaviours by changes in the composition and spatial organization of the cytoskeleton and by changes in nuclear mechanics. Our study highlights the need to combine rheology techniques for potential diagnostic or prognostic methods based on cancer cell mechanophenotyping.
Analyses of Biomarker Traits in Diverse UK Biobank Participants Identify Associations Missed by European-centric Analysis Strategies
Authors: Sun Quan , Graff Misa , Rowland Bryce , Wen Jia , Huang Le , Lee Moa P. , Avery Christy L. , Franceschini Nora , North Kari E. , Li Yun , Raffield Laura M. 
Published: September 2020

AbstractDespite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effect size associations being missed. Here, we conducted genome-wide association studies (GWAS) of 31 serum and urine biomarker quantitative traits in African (n=9354), East Asian (n=2559) and South Asian (n=9823) UK Biobank participants ancestry. We adjusted for all known GWAS catalog variants for each trait, as well as novel signals identified in European ancestry UK Biobank participants alone. We identify 12 novel signals in African ancestry and 3 novel signals in South Asian participants (p<1.61 × 10−10). Many of these signals are highly plausible and rare in Europeans (1% or lower minor allele frequency), includingcispQTLs for the genes encoding serum biomarkers like gamma-glutamyl transferase and apolipoprotein A,PIEZ01andG6PDvariants with impacts on HbA1c through likely erythocytic mechanisms, and a coding variant inGPLD1, a gene which cleaves GPI-anchors, associated with normally GPI-anchored protein alkaline phosphatase in serum. This work illustrates the importance of using the genetic data we already have in diverse populations, with many novel discoveries possible in even modest sample sizes.
Tractable models of ecological assembly
Authors: Serván Carlos A. , Allesina Stefano 
Published: September 2020

AbstractEcological assembly, the way natural communities form under ecological time-scales, is a fundamental and yet poorly understood process. Recent theoretical and empirical approaches to assembly consider systems in which a group of species is introduced in a new environment, and dynamics prune the system down to a sub-community of coexisting species. This “top-down” assembly approach contrasts with the well-studied “bottom-up”, or sequential, assembly, in which species from a pool enter the system one at a time, giving rise to priority effects and complex dynamics. Here we determine under which conditions the two approaches are equivalent, i.e., lead asymptotically to the same exact set of coexisting species. To achieve this result, we represent the assembly process as a network in which nodes are sub-communities and edges stand for invasions shifting the composition of the ecological community from a stable configuration to another. This abstraction makes it easy to determine which states the community can occupy, as well as highlight the potential for priority effects or cyclic species composition. We discuss how the equivalence between bottom-up and top-down assembly can advance our understanding of this challenging process from an empirical and theoretical point of view, informing the study of ecological restoration and the design and control of ecological communities.