bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis of the ventricular-subventricular zone reveals signatures of dorsal and ventral adult neurogenic lineages
Authors: Redmond Stephanie A. , Silla Arantxa Cebrian , Nascimento Marcos Assis , Mansky Benjamin , Wu David , Obernier Kirsten , Rodriguez Ricardo Romero , Lim Daniel A. , Alvarez-Buylla Arturo 
Published: February 2021

AbstractThe ventricular-subventricular zone (V-SVZ) is home to the largest neurogenic niche in the adult mouse brain. Previous work has demonstrated that resident stem cells in different locations within the V-SVZ produce different subtypes of new neurons for the olfactory bulb. While great progress has been made in understanding the differences in regional stem cell potential using viral and genetic lineage tracing strategies, the core molecular heterogeneity that underlies these regional differences is largely unknown. Here we present single whole-cell and single nucleus sequencing datasets of microdissected adult mouse V-SVZ, and evidence for the existence of two broad populations of adult neural stem cells. By using spatially resolved microdissections in the single nucleus sequencing dataset as a reference, and mapping marker gene expression in the V-SVZ, we find that these two populations reside in largely non-overlapping domains in either the dorsal or ventral V-SVZ. Furthermore, we identified two subpopulations of newly born neurons that have gene expression consistent with dorsal or ventral origins. Finally, we identify genes expressed by both stem cells and the neurons they generate that specifically mark either the dorsal or ventral adult neurogenic lineage. These datasets, methods and findings will facilitate the study of region-specific regulation of adult neurogenesis.
A Multiscale, Systems-level, Neuropharmacological Model of Cortico-Basal Ganglia System for Arm Reaching under Normal, Parkinsonian and Levodopa Medication Conditions
Authors: Nair Sandeep Sathyanandan , Muddapu Vignayanandam Ravindernath , Chakravarthy V. Srinivasa 
Published: February 2021

ABSTRACTThe root cause of Parkinson’s disease (PD) is the death of dopaminergic neurons in Substantia Nigra pars compacta (SNc). The exact cause of this cell death is still not known. Loss of SNc cells manifest as the cardinal symptoms of PD, including tremor, rigidity, bradykinesia, and postural imbalance. To investigate the PD condition in detail and understand the link between loss of cells in SNc and PD symptoms, it is important to have an integrated multiscale computational model that can replicate the symptoms at the behavioural level by evoking the key cellular and molecular underlying mechanisms that contribute to the pathology. In line with this objective, we present a multiscale integrated model of cortico-basal ganglia motor circuitry for arm reaching task, incorporating a detailed biophysical model of SNc dopaminergic neuron. Earlier researchers have shown that fluctuations in dopamine (DA) signals are analogous to reward/punishment signals, thereby prompting application of concepts from reinforcement learning (RL) to modelling the basal ganglia system. In our model, we replace the abstract representations of reward with the realistic variable of extracellular DA released by a network of SNc cells and incorporate it with the RL-based behavioural model, which simulates the arm reaching task. Our results showed that as SNc cell loss increases, the percentage success rate to reach the target decreases, and average time to reach the target increases. With levodopa (L-DOPA) medication, both the success rate and the average time to reach the target improved significantly. The proposed model also exhibits how differential dopaminergic axonal degeneration in basal ganglia results in various cardinal symptoms of PD as manifest in reaching movements. From the model results, we were able to show the side effects of L-DOPA mediation, such as wearing off and peak dosage dyskinesias. Moreover, from the results, we were able to predict the optimum dosage for varying degrees of cell loss and L-DOPA medication. The proposed model has a potential clinical application where drug dosage can be optimized as per patient characteristics. We conclude that our model presents a realistic and efficient way of simulating the PD pathology conditions and the effect of levodopa medication, thereby giving a reliable indicator towards the optimization of the drug dosage.
Genome-Wide Identification of 5-Methylcytosine Sites in Bacterial Genomes By High-Throughput Sequencing of MspJI Restriction Fragments
Authors: Anton Brian P. , Fomenkov Alexey , Wu Victoria , Roberts Richard J. 
Published: February 2021

ABSTRACTSingle-molecule Real-Time (SMRT) sequencing can easily identify sites of N6-methyladenine and N4-methylcytosine within DNA sequences, but similar identification of 5-methylcytosine sites is not as straightforward. In prokaryotic DNA, methylation typically occurs within specific sequence contexts, or motifs, that are a property of the methyltransferases that “write” these epigenetic marks. We present here a straightforward, cost-effective alternative to both SMRT and bisulfite sequencing for the determination of prokaryotic 5-methylcytosine methylation motifs. The method, called MFRE-Seq, relies on excision and isolation of fully methylated fragments of predictable size using MspJI-Family Restriction Enzymes (MFREs), which depend on the presence of 5-methylcytosine for cleavage. We demonstrate that MFRE-Seq is compatible with both Illumina and Ion Torrent sequencing platforms and requires only a digestion step and simple column purification of size-selected digest fragments prior to standard library preparation procedures. We applied MFRE-Seq to numerous bacterial and archaeal genomic DNA preparations and successfully confirmed known motifs and identified novel ones. This method should be a useful complement to existing methodologies for studying prokaryotic methylomes and characterizing the contributing methyltransferases.
An opposing self-reinforced odor pre-exposure memory produces latent inhibition inDrosophila
Authors: Jacob Pedro F. , Vargas-Gutierrez Paola , Okray Zeynep , Vietti-Michelina Stefania , Felsenberg Johannes , Waddell Scott 
Published: February 2021

AbstractPrior experience of a stimulus can inhibit subsequent acquisition or expression of a learned association of that stimulus. However, the neuronal manifestations of this learning effect, named latent inhibition (LI), are poorly understood. Here we show that odor pre-exposure produces LI of appetitive olfactory memory performance inDrosophila. Behavioral expression of LI requires that the context during memory testing resembles that during the odor pre-exposures. Odor pre-exposure forms an aversive memory that requires dopaminergic neurons that innervate the γ2α′1 and α3 mushroom body compartments - those to α3 exhibit increasing odor-driven activity with successive pre-exposures. In contrast, odor-specific responses of the corresponding mushroom body output neurons are suppressed. Odor pre-exposure therefore recruits specific dopaminergic neurons that provide teaching signals that attach negative valence to the odor itself. LI ofDrosophilaappetitive memory consequently results from a temporary and context-dependent retrieval deficit imposed by competition with this short-lived aversive memory.
Effects of physical, chemical, and biological ageing on the mineralization of pine wood biochar by aStreptomycesisolate
Authors: Zeba Nayela , Berry Timothy D. , Whitman Thea L. 
Published: February 2021

AbstractIf biochar is to be used for carbon (C) management, we must understand how ageing affects biochar C mineralization. Here, we incubated aged and unaged eastern white pine wood biochar produced at 350 and 550 °C with aStreptomycesisolate, a putative biochar-decomposing microbe. Ageing was simulated via exposure to (a) alternating freeze-thaw and wet-dry cycles (physical ageing), (b) concentrated hydrogen peroxide (chemical ageing) and (c) nutrients and microorganisms (biological ageing). Elemental composition and surface chemistry (Fourier Transform Infrared spectroscopy) of biochar samples were compared before and after ageing. Ageing significantly increased biochar C mineralization in the case of physically aged 350 °C biochar (p < 0.001). Among 350 °C biochars, biochar C mineralization was positively correlated with an increase in O/C ratio (R2= 0.78) and O-containing functional groups (R2= 0.73) post-ageing, suggesting that surface oxidation during ageing enhanced biochar degradation by the isolate. However, in the case of 550 °C biochar, ageing did not result in a significant change in biochar C mineralization (p > 0.05), likely due to lower surface oxidation and high condensed aromatic C content. These results have implications for the use of biochar for long term C storage in soils.SynopsisThis study highlights the impact of ageing on the microbial mineralization of biochar, which can affect its long-term C storage capacity.TOC Graphic
A comprehensive urine proteome database generated from patients with various renal conditions and prostate cancer
Authors: Swensen Adam C. , He Jingtang , Fang Alexander C. , Ye Yinyin , Nicora Carrie D. , Shi Tujin , Liu Alvin Y. , Sigdel Tara K. , Sarwal Minnie M. , Qian Wei-Jun 
Published: February 2021

AbstractUrine proteins can serve as viable biomarkers for diagnosing and monitoring various diseases. A comprehensive urine proteome database, generated from a variety of urine samples with different disease conditions, can serve as a reference resource for facilitating discovery of potential urine protein biomarkers. Herein, we present a urine proteome database generated from multiple datasets using 2D LC-MS/MS proteome profiling of urine samples from healthy individuals (HI), renal transplant patients with acute rejection (AR) and stable graft (STA), patients with non-specific proteinuria (NS), and patients with prostate cancer (PC). A total of ~28,000 unique peptides spanning ~2,200 unique proteins were identified with a false discovery rate of <0.5% at the protein level. Over one third of the annotated proteins were plasma membrane proteins and another one third were extracellular proteins according to gene ontology analysis. Ingenuity Pathway Analysis of these proteins revealed 349 potential biomarkers. Surprisingly, 43% (167) of all known cluster of differentiation (CD) proteins were identified in the various human urine samples. Interestingly, following comparisons with five recently published urine proteome profiling studies, which applied similar approaches, there are still ~400 proteins which are unique to this current study. These may represent potential disease-associated proteins. Among them, several proteins such as myoglobin, serpin B3, renin receptor, and periostin have been reported as pathological markers for renal failure and prostate cancer, respectively. Taken together, our data should provide valuable information for future discovery and validation studies of urine protein biomarkers for various diseases.
PXC2, a polarized receptor kinase, functions to repress ground tissue cell divisions and restrict stele size
Authors: Goff Jason , Rony R. M. Imtiaz Karim , Ge Zengxiang , Hajný Jakub , Rodriguez-Furlan Cecilia , Friml Jiri , Van Norman Jaimie M. 
Published: February 2021

ABSTRACTCoordination of cell division and differentiation is critical for tissue patterning during organ development. Directional signaling and cell polarity have important roles in coordination of these processes. For instance, the Arabidopsis receptor-like kinase INFLORESCENCE AND ROOT APICES KINASE (IRK) functions to restrict stele area and repress longitudinal anticlinal divisions (LADs) in the endodermis where it is polarly localized. IRK is closely related to PXY/TDR CORRELATED 2 (PXC2); here, we show that PXC2 exhibits similar polarized accumulation suggesting they have related functions.pxc2roots have increased stele area andirk pxc2double mutant roots show increases in stele area and endodermal LADs beyond either single mutant, indicating that polarly localized IRK and PXC2 function redundantly to repress endodermal LADs and stele area. The double mutant also exhibits agravitropic root growth and abnormal cotyledon vein patterning. Manipulation of PIN1 trafficking and (re)localization mechanisms indicate that PXC2 and/or IRK suggest a link to modulation of polar auxin transport. We conclude that IRK and PXC2 have partially redundant functions in the root, but may have independent functions that are tissue-specific. We propose that repression of endodermal LADs and stele area through a PXC2/IRK-mediated, directional signaling pathway is required for normal ground tissue cell divisions, tissue patterning, and growth in Arabidopsis roots.
Action-based predictions affect visual perception, neural processing, and pupil size, regardless of temporal predictability
Authors: Lubinus Christina , Einhäuser Wolfgang , Schiller Florian , Kircher Tilo , Straube Benjamin , van Kemenade Bianca M. 
Published: February 2021

AbstractSensory consequences of one’s own action are often perceived as less intense, and lead to reduced neural responses, compared to externally generated stimuli. Presumably, such sensory attenuation is due to predictive mechanisms based on the motor command (efference copy). However, sensory attenuation has also been observed outside the context of voluntary action, namely when stimuli are temporally predictable. Here, we aimed at disentangling the effects of motor and temporal predictability-based mechanisms on the attenuation of sensory action consequences. During fMRI data acquisition, participants (N = 25) judged which of two visual stimuli was brighter. In predictable blocks, the stimuli appeared temporally aligned with their button press (active) or aligned with an automatically generated cue (passive). In unpredictable blocks, stimuli were presented with a variable delay after button press/cue, respectively. Eye tracking was performed to investigate pupil-size changes and to ensure proper fixation. Self-generated stimuli were perceived as darker and led to less neural activation in visual areas than their passive counterparts, indicating sensory attenuation for self-generated stimuli independent of temporal predictability. Pupil size was larger during self-generated stimuli, which correlated negatively with blood oxygenation level dependent (BOLD) response: the larger the pupil, the smaller the BOLD amplitude in visual areas. Our results suggest that sensory attenuation in visual cortex is driven by action-based predictive mechanisms rather than by temporal predictability. This effect may be related to changes in pupil diameter. Altogether, these results emphasize the role of the efference copy in the processing of sensory action consequences.
Mitochondrial F1FOATP synthase determines the local proton motive force in cristae tips
Authors: Rieger Bettina , Arroum Tasnim , Villalta Jimmy , Busch Karin B. 
Published: February 2021

ABSTRACTThe classical view of oxidative phosphorylation is that a proton motive force PMF generated by the respiratory chain complexes fuels ATP synthesis. Under glycolytic conditions, ATP synthase in its reverse mode also can contribute to the PMF. Here, we dissected the two functions of ATP synthase and the role of its inhibitory factor 1 (IF1) under different metabolic conditions in detail. pH profiles of mitochondrial sub-compartments were recorded with high spatial resolution in live mammalian cells by positioning a pH-sensor directly at F1and FOof ATP synthase, complex IV and in the matrix. Our results clearly show that ATP synthase activity is substantially controlling the PMF and that IF1 is essential under OXPHOS conditions to prevent reverse ATP synthase activity due to an almost negligible ΔpH.GRAPHICAL ABSTRACTHIGHLIGHTSThe ΔpH along and across the inner mitochondrial membrane is not homogeneousThe proton motive force at cristae tips is controlled by F1FOATP synthaseUnder OXPHOS conditions, the pH difference between FOand F1of active ATP synthase is almost negligible (1.2 proton vs. 1 proton equivalent)IF1 is required to prevent the onset of ATP hydrolysis under OXPHOS conditions
Ribovore: ribosomal RNA sequence analysis for GenBank submissions and database curation
Authors: Schäffer Alejandro A. , McVeigh Richard , Robbertse Barbara , Schoch Conrad L. , Johnston Anjanette , Underwood Beverly A. , Karsch-Mizrachi Ilene , Nawrocki Eric P. 
Published: February 2021

AbstractBackgroundThe DNA sequences encoding ribosomal RNA genes (rRNAs) are commonly used as markers to identify species, including in metagenomics samples that may combine many organismal communities. The 16S small subunit ribosomal RNA (SSU rRNA) gene is typically used to identify bacterial and archaeal species. The nuclear 18S SSU rRNA gene, and 28S large subunit (LSU) rRNA gene have been used as DNA barcodes and for phylogenetic studies in different eukaryote taxonomic groups. Because of their popularity, the National Center for Biotechnology Information (NCBI) receives a disproportionate number of rRNA sequence submissions and BLAST queries. These sequences vary in quality, length, origin (nuclear, mitochondria, plastid), and organism source and can represent any region of the ribosomal cistron.ResultsTo improve the timely verification of quality, origin and loci boundaries, we developed Ribovore, a software package for sequence analysis of rRNA sequences. Theribotyperandribosensorprograms are used to validate incoming sequences of bacterial and archaeal SSU rRNA. Theribodbmakerprogram is used to create high-quality datasets of rRNAs from different taxonomic groups. Key algorithmic steps include comparing candidate sequences against rRNA sequence profile hidden Markov models (HMMs) and covariance models of rRNA sequence and secondary-structure conservation, as well as other tests. Nine freely availableblastnrRNA databases created and maintained with Ribovore are used for checking incoming GenBank submissions and used by theblastnbrowser interface at NCBI. Since 2018, Ribovore has been used to analyze more than 50 million prokaryotic SSU rRNA sequences submitted to GenBank, and to select at least 10,435 fungal rRNA RefSeq records from type material of 8,350 taxa.ConclusionRibovore combines single-sequence and profile-based methods to improve GenBank processing and analysis of rRNA sequences. It is a standalone, portable, and extensible software package for the alignment, classification and validation of rRNA sequences. Researchers planning on submitting SSU rRNA sequences to GenBank are encouraged to download and use Ribovore to analyze their sequences prior to submission to determine which sequences are likely to be automatically accepted into GenBank.
Accelerating COVID-19 research with graph mining and transformer-based learning
Authors: Tyagin Ilya , Kulshrestha Ankit , Sybrandt Justin , Matta Krish , Shtutman Michael , Safro Ilya 
Published: February 2021

ABSTRACTIn 2020, the White House released the, “Call to Action to the Tech Community on New Machine Readable COVID-19 Dataset,” wherein artificial intelligence experts are asked to collect data and develop text mining techniques that can help the science community answer high-priority scientific questions related to COVID-19. The Allen Institute for AI and collaborators announced the availability of a rapidly growing open dataset of publications, the COVID-19 Open Research Dataset (CORD-19). As the pace of research accelerates, biomedical scientists struggle to stay current. To expedite their investigations, scientists leverage hypothesis generation systems, which can automatically inspect published papers to discover novel implicit connections. We present an automated general purpose hypothesis generation systems AGATHA-C and AGATHA-GP for COVID-19 research. The systems are based on graph-mining and the transformer model. The systems are massively validated using retrospective information rediscovery and proactive analysis involving human-in-the-loop expert analysis. Both systems achieve high-quality predictions across domains (in some domains up to 0.97% ROC AUC) in fast computational time and are released to the broad scientific community to accelerate biomedical research. In addition, by performing the domain expert curated study, we show that the systems are able to discover on-going research findings such as the relationship between COVID-19 and oxytocin hormone.ReproducibilityAll code, details, and pre-trained models are available athttps://github.com/IlyaTyagin/AGATHA-C-GPCCS CONCEPTS•Applied computing→Bioinformatics;Document management and text processing; •Computing methodologies→Learning latent representations;Neural networks;Information extraction;Semantic networks.
Antibody ligation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), CEACAM3, and CEACAM6, differentially enhance the cytokine release of human neutrophils in responses toCandida albicans
Authors: Klaile Esther , Prada Salcedo Juan Pablo , Klassert Tilman E. , Besemer Matthias , Bothe Anne-Katrin , Durotin Adrian , Müller Mario M. , Schmitt Verena , Luther Christian H. , Dittrich Marcus , Singer Bernhard B. , Dandekar Thomas , Slevogt Hortense 
Published: February 2021

AbstractInvasive candidiasis, often caused byCandida albicans, is an important healthcare-associated fungal infection that results in a high mortality rate of up to 40%. Neutrophils are the first line of defense during Candida infections. They can initiate various killing mechanisms and release cytokines to attract further immune cells to the site of infection. These responses are tightly controlled, since they can also lead to severe tissue/organ damage. We hypothesized that the regulation ofC. albicans-specific neutrophil functions by the immunoregulatoryC. albicansreceptors CEACAM1, CEACAM3, and CEACAM6 are involved in the immune pathology of candidemia. Here, we analyzed the effects of the specific antibodies B3-17, 308/3-3, and 1H7-4B, respectively, targeting the three CEACAM receptors onC. albicans-induced neutrophil responses. We show that ligation of CEACAM6 significantly enhanced the response toC. albicans, as evidenced by the increased CXCL8/IL-8 secretion. By assessing the transcriptional responses, we found that CEACAM6 ligation and to some extent CEACAM1 ligation, but not CEACAM3 ligation, resulted in altered gene regulation of theC. albicans-stimulated neutrophils. Genes that were differentially regulated by the different CEACAM-targeting antibodies were analyzed for affected cellular processes and signaling pathways using various bioinformatics methods, including integrated network analyses and dynamic simulations of signaling cascades. Predicted changes in cellular pathways and cellular functions included CEACAM-specific alterations in apoptosis and cytokine secretion. In particular, we verified predicted changes in IL-1β/IL-6 expression in response to the antibody ligation of all three targeted CEACAMs and apoptosis induction by anti-CEACAM6 antibody treatment in presence ofC. albicansstimulation. Specifically, CEACAM6 ligation by 1H7-4B enhanced neutrophil apoptosis and increased immediate and long-term cytokine release in responses toC. albicans. CEACAM1 ligation by B3-17 mainly enhanced the immediate secretion of pro-inflammatory cytokines, and CEACAM3 ligation by 308/3-3 increased the long-term release of pro-inflammatory cytokines. Taken together, we demonstrated for the first time that CEACAM receptors have an important and differential impact on the regulation ofC. albicans-induced immune functions in human neutrophils.