bluuebunny/crossref_metadata_2025_split huggingface dataset:
ToxCast chemical library screen identifies diethanolamine as an activator of Wnt signaling
Authors: Wolter Justin M. , Jimenez Jessica A. , Stein Jason L. , Zylka Mark J. 
Published: February 2021

AbstractNumerous autism spectrum disorder (ASD) risk genes are associated with Wnt signaling, suggesting that brain development may be especially sensitive to genetic perturbation of this pathway. Additionally, valproic acid, which modulates Wnt signaling, increases risk for ASD when taken during pregnancy. We previously found that an autism-linked gain-of-function UBE3AT485Amutant construct hyperactivated canonical Wnt signaling, providing a genetic means to elevate Wnt signaling above baseline levels. To identify environmental use chemicals that enhance or suppress Wnt signaling, we screened the ToxCast Phase I and II libraries in cells expressing this autism linkedUBE3AT485gain-of-function mutant construct. Using structural comparisons, we identify classes of chemicals that stimulated Wnt signaling, including ethanolamines, as well as chemicals that inhibited Wnt signaling, such as agricultural pesticides, and synthetic hormone analogs. To prioritize chemicals for follow-up, we leveraged predicted human exposure data, and identified diethanolamine (DEA) as a chemical that both stimulates Wnt signaling inUBE3AT485A–transfected cells and has a high potential for prenatal exposure in humans. DEA also enhanced proliferation in two primary human neural progenitor cell lines. Overall, this study identifies chemicals with the potential for human exposure that influence Wnt signaling in human cells.
Magnetically stimulated cryogels to enhance osteogenic and chondrogenic differentiation of stem cells
Authors: Odabas Sedat , Tevlek Atakan , Erenay Berkay , Aydın Halil Murat , Süloglu Aysun Kılıç , Saglam Atiye Seda Yar , Garipcan Bora 
Published: February 2021

AbstractCells can respond to the physical stimulus that comes from their micro-environments. There are several strategies to alter cell behavior. Several tissues like bone and cartilage, which are the point of interest of regenerative medicine, are under significant degrees of mechanical stress in real life. Within this stress, the arising mechanotransduction effect may trigger several behavioral responses on cells. As a novel and efficient way, magnetic nanoparticles can be used to make such a mechanotransductive effect on cells.In this study, pre-functionalized Fe3O4superparamagnetic magnetite nanoparticles were synthesized and used to fabricate gelatin-based magnetic cryogels. Cell growth, tissue-specific metabolic activities, differentiation potential to the bone, and cartilage under static magnetic field at different magnetic field strength (1000-4000G) were investigated. Results indicated that there was a better induction in considerable higher magnetic field among all others and magnetic cryogels helps to mediate mesenchymal stem cell behaviour, promote their growth and induce osteogenic and chondrogenic differentiation.
PandoraGAN: Generating antiviral peptides using Generative Adversarial Network
Authors: Surana Shraddha , Arora Pooja , Singh Divye , Sahasrabuddhe Deepti , Valadi Jayaraman 
Published: February 2021

AbstractThe continuous increase in pathogenic viruses and the intensive laboratory research emphasizes the need for cost and time efficient drug development. This accelerates research for alternate drug candidates like antiviral peptides(AVP) that have therapeutic and prophylactic potential and gaining attention in recent times. However, diversity in their sequences, limited and non-uniform characterization often limit their applications. Isolating newer peptide backbones with required characteristics is a cumbersome process with many design-test-build cycles. Advanced deep learning approaches such as generative adversarial networks (GAN) can be helpful to expedite the initial stage of developing novel peptide drugs. In this study, we developed PandoraGAN that uses a manually curated training dataset of 130 highly active peptides that includes peptides from known databases (such as AVPdb) and literature to generate novel antiviral peptides. The underlying architecture in PandoraGAN is able to learn a good representation of the implicit properties of antiviral peptides. The generated sequences from PandoraGAN are validated based on physico-chemical properties. They are also compared with the training dataset statistically using Pearson’s correlation and Mann-Whitney U-test. We therefore confirm that PandoraGAN is capable of generating a novel antiviral peptide backbone showing similar properties to that of the known highly active antiviral peptides. This approach exhibits a potential to discover novel patterns of AVP which may have not been seen earlier with traditional methods. To our knowledge this is the first ever use of GAN models for antiviral peptides across the viral spectrum.
Changes of mind after movement onset: a motor-state dependent decision-making process
Authors: Cos Ignasi , Pezzulo Giovanni , Cisek Paul 
Published: February 2021

ABSTRACTDecision-making is traditionally described as a cognitive process of deliberation followed by commitment to an action choice, preceding the planning and execution of the chosen action. However, this is challenged by recent data suggesting that multiple options are specified simultaneously and compete in pre-motor cortical areas for selection and execution. Previous studies focused on the competition during planning, and leave unaddressed the dynamics of decisions during movement. Does deliberation extend into the execution phase? Are non-selected options still considered? Here we studied a decision-making task in which human participants were instructed to select a reaching path trajectory from an origin to a rectangular target, where reward was distributed non-uniformly at the target. Critically, we applied mechanical perturbations to the arm during movement to study under which conditions such perturbations produce changes of mind. Our results show that participants initially selected the direction of movement towards the highest reward region, and changed their mind most frequently when the two choices offered the same reward, showing that deliberation continues and follows cost-benefit considerations during movement. Furthermore, changes of mind were dependent upon the intensity of the perturbation and the current state of the motor system, including velocity and distance to targets. Although reward remains most relevant, our results indicate that the state of the motor system when the perturbation occurs is a crucial determinant of changes of mind. This indicates that the neural circuits that assess reward and those that control movements operate synergistically rather than sequentially during decision-making.Significance StatementOur study provides supporting evidence for the notion that deliberation during decision-making continues after movement onset because unselected potential actions are not completely suppressed or discarded. From a neurophysiological perspective, our findings suggest that the competition between actions is not over before action initiation, possibly because the initially unselected neuronal population retains some sub-threshold activation, which enables them to take control afterwards. Furthermore, our findings also suggest that decision-makers have a variable degree of commitment to their initial choice, which depends on the relative reward of the offers and on the state of the motor system. The commitment is stronger if the initially selected plan leads to higher rewards, and changes of mind occur more frequently if the velocity and relative position of the end-point are within specific ranges.
Primary motor cortex activity traces distinct trajectories of population dynamics during spontaneous facial motor sequences in mice
Authors: Boffi Juan Carlos , Wiessalla Tristan , Prevedel Robert 
Published: February 2021

AbstractWe explore the link between on-going neuronal activity at primary motor cortex (M1) and face movement in awake mice. By combining custom-made behavioral sequencing analysis and fast volumetric Ca2+-imaging, we simultaneously tracked M1 population activity during many different facial motor sequences. We show that a facial area of M1 displays distinct trajectories of neuronal population dynamics across different spontaneous facial motor sequences, suggesting an underlying population dynamics code.Significance statementHow our brain controls a seemingly limitless diversity of body movements remains largely unknown. Recent research brings new light into this subject by showing that neuronal populations at the primary motor cortex display different dynamics during forelimb reaching movements versus grasping, which suggests that different motor sequences could be associated with distinct motor cortex population dynamics. To explore this possibility, we designed an experimental paradigm for simultaneously tracking the activity of neuronal populations in motor cortex across many different motor sequences. Our results support the concept that distinct population dynamics encode different motor sequences, bringing new insight into the role of motor cortex in sculpting behavior while opening new avenues for future research.
High-pressure sprayed siRNAs influence the efficiency but not the profile of transitive silencing
Authors: Uslu Veli Vural , Dalakouras Athanasios , Steffens Victor A , Krczal Gabi , Wassenegger Michael 
Published: February 2021

SUMMARYIn plants, small interfering RNAs (siRNAs) are a quintessential class of RNA interference (RNAi)-inducing molecules produced by the endonucleolytic cleavage of double stranded RNAs (dsRNAs). In order to ensure robust RNAi, siRNAs are amplified through a positive feedback mechanism called transitivity. Transitivity relies on RNA-DIRECTED-RNA POLYMERASE 6 (RDR6)-mediated dsRNA synthesis using siRNA-targeted RNA. The newly synthesized dsRNA is subsequently cleaved into secondary siRNAs by DICER-LIKE (DCL) endonucleases. Just like primary siRNAs, secondary siRNAs are also loaded into ARGONAUTE proteins (AGOs) to form an RNA-induced silencing complex (RISC) reinforcing the cleavage of the target RNA. Although the molecular players underlying transitivity are well established, the mode of action of transitivity remains elusive. In this study, we investigated the influence of primary target sites on transgene silencing and transitivity using the GFP-expressingNicotiana benthamiana16C line, high pressure spraying protocol (HPSP), and synthetic 22-nucleotide (nt) long siRNAs. We found that the 22-nt siRNA targeting the 3’ of the GFP transgene was less efficient in inducing silencing when compared to the siRNAs targeting the 5’ and middle region of the GFP. Moreover, sRNA sequencing of locally silenced leaves showed that the amount but not the profile of secondary RNAs is shaped by the occupancy of the primary siRNA triggers on the target RNA. Our findings suggest that RDR6-mediated dsRNA synthesis is not primed by primary siRNAs and that dsRNA synthesis appears to be generally initiated at the 3’ end of the target RNA.SIGNIFICANCE STATEMENTThis work answers a long-standing question about the role of siRNA triggers in initiating transitive silencing. By using high-pressure spraying-mediated delivery of synthetic siRNAs, we provided experimental evidence that target position of 22-nt-long primary siRNAs influences the efficiency of RDR6-driven double stranded RNA (dsRNA) synthesis, but it does not change the profile of accumulating secondary siRNAs originating from processing of RDR6-produced dsRNA.
On the phenology of protists: Recurrent patterns reveal seasonal variation of protistan (Rhizaria: Cercozoa, Endomyxa) communities in tree canopies
Authors: Walden Susanne , Jauss Robin-Tobias , Feng Kai , Fiore-Donno Anna Maria , Dumack Kenneth , Schaffer Stefan , Wolf Ronny , Schlegel Martin , Bonkowski Michael 
Published: February 2021

AbstractTree canopies are colonized by billions of highly specialized microorganisms that are well adapted to the extreme microclimatic conditions, caused by diurnal fluctuations and seasonal changes. In this study we investigated seasonality patterns of protists in tree canopies of a temperate floodplain forest via high-throughput sequencing with group-specific primers for the phyla Cercozoa and Endomyxa. We observed consistent seasonality and identified divergent spring and autumn taxa. Tree crowns were characterized by a dominance of bacterivores and omnivores, while eukaryvores gained a distinctly larger share in litter and soil communities on the ground. Seasonality was largest among communities detected on the foliar surface. Higher variance within alpha diversity of foliar communities in spring indicated greater heterogeneity during community assembly. However, communities underwent distinct changes during the aging of leaves in autumn, reflecting recurring phenological changes during microbial colonization of leaves. Surprisingly, endomyxan root pathogens appeared to be exceptionally abundant across tree canopies during autumn season, demonstrating a potential role of the canopy surface as an important reservoir for wind-dispersed propagules. Overall, about 80% of detected OTUs could not be assigned to known species – representing only a fraction of dozens of microeukaryotic taxa whose canopy inhabitants are waiting to be discovered.
Simulating the emergence of the Visual Word Form Area: Recycling a convolutional neural network for reading
Authors: Hannagan T. , Agrawal A. , Cohen L. , Dehaene S. 
Published: February 2021

AbstractThe visual word form area (VWFA) is a region of human inferotemporal cortex that emerges at a fixed location in occipitotemporal cortex during reading acquisition, and systematically responds to written words in literate individuals. According to the neuronal recycling hypothesis, this region arises through the repurposing, for letter recognition, of a subpart of the ventral visual pathway initially involved in face and object recognition. Furthermore, according to the biased connectivity hypothesis, its universal localization is due to pre-existing connections from this subregion to areas involved in spoken language processing. Here, we evaluate those hypotheses in an explicit computational model. We trained a deep convolutional neural network of the ventral visual pathway, first to categorize pictures, and then to recognize written words invariantly for case, font and size. We show that the model can account for many properties of the VWFA, particularly when a subset of units possesses a biased connectivity to word output units. The network develops a sparse, invariant representation of written words, based on a restricted set of reading-selective units. Their activation mimics several properties of the VWFA, and their lesioning causes a reading-specific deficit. Our simulation fleshes out the neuronal recycling hypothesis, and make several testable predictions concerning the neural code for written words.
A deep learning model for fish classification base on DNA barcode
Authors: Jin Lina , Yu Jiong , Yuan Xiaoqian , Du Xusheng 
Published: February 2021

AbstractFish is one of the most extensive distributed organisms in the world, fish taxonomy is an important part of biodiversity and is also the basis of fishery resources management. However, the morphological characters are so subtle to identify and intact specimens are not available sometimes, making the research and application of morphological method laborious and time-consuming. DNA barcoding based on a fragment of the cytochrome c oxidase subunit I (COI) gene is a valuable molecular tool for species identification and biodiversity studies. In this paper, a novel deep learning classification approach that fuses Elastic Net-Stacked Autoencoder (EN-SAE) with Kernel Density Estimation (KDE), named ESK-model, is proposed bases on DNA barcode. In stage one, ESK-model preprocesses the original data from COI fragments. In stage two, EN-SAE is used to learn the deep features and obtain the outgroup score of each fish. In stage three, KDE is used to select the threshold base on the outgroup scores and classify fish from different families. The effectiveness and superiority of ESK-model have been validated by experiment on three dominant fish families and comparisons with state-of-the-art methods. Those findings confirm that the ESK-model can accurately classify fish from different family base on DNA barcode.
Comparative genome analysis revealed gene inversions, boundary expansion and contraction, and gene loss inStemona sessilifolia(Miq.) Miq. chloroplast genome
Authors: Liu Jingting , Jiang Mei , Chen Haimei , Liu Yu , Liu Chang , Wu Wuwei 
Published: February 2021

AbstractStemona sessilifolia(Miq.) Miq., commonly known as Baibu, is one of the most popular herbal medicines in Asia. In Chinese Pharmacopoeia, Baibu has multiple authentic sources, and there are many homonym herbs sold as Baibu in the herbal medicine market. The existence of the counterfeits of Baibu brings challenges to its identification. To assist the accurate identification of Baibu, we sequenced and analyzed the complete chloroplast genome ofStemona sessilifoliausing next-generation sequencing technology. The genome was 154,039 bp in length, possessing a typical quadripartite structure consisting of a pair of inverted repeats (IRs: 27,094 bp) separating by a large single copy (LSC: 81,950 bp) and a small single copy (SSC: 17,901 bp). A total of 112 unique genes were identified, including 80 protein-coding, 28 transfer RNA, and four ribosomal RNA genes. Besides, 45 tandem, 27 forward, 23 palindromic, and 72 simple sequence repeats were detected in the genome by repeat analysis. Compared with its counterfeits(Asparagus officinalisandCarludovica palmate), we found that IR expansion and SSC contraction events ofStemona sessilifoliaresulted in two copies ofthe rpl22gene in the IR regions and partial duplication of thendhFgene in the SSC region. Secondly, an approximately 3-kb-long inversion was identified in the LSC region, leading tothe petAandcemAgene presented in the complementary strand of the chloroplast DNA molecule. Comparative analysis revealed some highly variable regions, includingtrnF-GAA_ndhJ, atpB_rbcL, rps15_ycf1, trnG-UCC_trnR-UCU, ndhF_rpl32.Finally, gene loss events were investigated in the context of phylogenetic relationships. In summary, the complete plastome ofStemona sessilifoliawill provide valuable information for the molecular identification of Baibu and assist in elucidating the evolution ofStemona sessilifolia.
Saccharomyces cerevisiaedeficient in the early anaphase release of Cdc14 can traverse anaphase I without ribosomal DNA disjunction and successfully complete meiosis
Authors: Yellman Christopher M. 
Published: February 2021

ABSTRACTEukaryotic meiosis is a specialized cell cycle involving two successive nuclear divisions that lead to the formation of haploid gametes. The phosphatase Cdc14 plays an essential role in meiosis as revealed in studies of the yeastSaccharomyces cerevisiae. Cdc14 is stored in the nucleolus, a sub-nuclear domain containing the ribosomal DNA, and its release is regulated by two distinct pathways, one acting in early anaphase I of meiosis and a second at the exit from meiosis II. The early anaphase release is thought to be important for disjunction of the ribosomal DNA, disassembly of the anaphase I spindle, spindle pole re-duplication and the counteraction of CDK, all of which are required for progression into meiosis II. The release of Cdc14 from its nucleolar binding partner Net1 is stimulated by phosphorylation of cyclin-dependent kinase sites in Net1, but the importance of that phospho-regulation in meiosis is not well understood. We inducednet1-6cdkmutant cells to enter meiosis and examined the localization of Cdc14 and various indicators of meiotic progression. Thenet1-6cdkmutations inhibit, but don’t fully prevent Cdc14 release, and they almost completely prevent disjunction of the ribosomal DNA during meiosis I. Failure to disjoin the ribosomal DNA is lethal in mitosis, and we expected the same to be true in meiosis. However, the cells were able to complete meiosis II, yielding the expected four meiotic products as viable spores. Therefore, all ribosomal DNA disjunction required for meiosis can occur in meiosis II. We discuss the implications of these findings for our understanding of meiotic chromosome segregation.
The shifting of dominating roles between structural cells and immune cells are key regulators of human adipose tissues aging
Authors: Zhou Wenyan , Lin Junxin , Hu Xueqing , Yao Xudong , Ouyang Hongwei 
Published: February 2021

AbstractAdipose tissue is a highly dynamic organ with complex cellular composition. Aging induces adipose tissue function decline and relocation of peripheral adipose tissue to abdominal compartment, which often associated with inflammation and metabolic disorders. Here we performed single-cell RNA sequencing to comprehensively and unbiasedly deconvolve how subcutaneous adipose tissue (SAT) responses to aging. We collected >25,000 stromal vascular cells from abdominal and gluteofemoral SAT of young and old donors. Analyses of transcription signatures and cell networks uncovered impaired adipogenesis and extracellular matrix synthesis capacity of APC, altered metabolic phenotype of immune cells and shifted tissue-dominating cells that can be used to predict adipose tissue aging. We also reported aging-associated distinct transcriptional program between gluteofemoral SAT and abdominal SAT. Our work thus reveals unanticipated cellular, immunological, metabolic and site-specific aspects of human adipose tissues aging process, providing valuable resource for better understanding of aging-associated adipose tissue dysfunction.
The dynamic transition of persistence towards the VBNC state during stationary phase is driven by protein aggregation
Authors: Dewachter Liselot , Bollen Celien , Wilmaerts Dorien , Louwagie Elen , Herpels Pauline , Matthay Paul , Khodaparast Ladan , Khodaparast Laleh , Rousseau Frederic , Schymkowitz Joost , Michiels Jan 
Published: February 2021

AbstractDecades of research into bacterial persistence has been unable to fully characterize this antibiotic-tolerant phenotype, thereby hampering the development of therapies effective against chronic infections. Although some active persister mechanisms have been identified, the prevailing view is that cells become persistent because they enter a dormant state. We therefore characterized starvation-induced dormancy inEscherichia coli. Our findings indicate that dormancy develops gradually; persistence strongly increases during stationary phase and decreases again as persisters enter the viable but nonculturable (VBNC) state. Importantly, we show that dormancy development is tightly associated with progressive protein aggregation, which occurs concomitantly with ATP depletion during starvation. Persisters contain protein aggregates in an early developmental stage while VBNC cells carry more mature aggregates. Finally, we show that at least one persister protein, ObgE, works by triggering aggregation and thereby changing the dynamics of persistence and dormancy development. These findings provide evidence for a genetically-controlled, gradual development of persisters and VBNC cells through protein aggregation.