bluuebunny/crossref_metadata_2025_split huggingface dataset:
DomBpred: protein domain boundary predictor using inter-residue distance and domain-residue level clustering
Authors: Yu Zhongze , Peng Chunxiang , Liu Jun , Zhang Biao , Zhou Xiaogen , Zhang Guijun 
Published: November 2021

AbstractDomain boundary prediction is one of the most important problems in the study of protein structure and function, especially for large proteins. At present, most domain boundary prediction methods have low accuracy and limitations in dealing with multi-domain proteins. In this study, we develop a sequence-based protein domain boundary predictor, named DomBpred. In DomBpred, the input sequence is firstly classified as either a single-domain protein or a multi-domain protein through a designed effective sequence metric based on a constructed single-domain sequence library. For the multi-domain protein, a domain-residue level clustering algorithm inspired by Ising model is proposed to cluster the spatially close residues according inter-residue distance. The unclassified residues and the residues at the edge of the cluster are then tuned by the secondary structure to form potential cut points. Finally, a domain boundary scoring function is proposed to recursively evaluate the potential cut points to generate the domain boundary. DomBpred is tested on a large-scale test set of FUpred comprising 2549 proteins. Experimental results show that DomBpred better performs than the state-of-the-art methods in classifying whether protein sequences are composed by single or multiple domains, and the Matthew’s correlation coefficient is 0.882. Moreover, on 849 multi-domain proteins, the domain boundary distance and normalised domain overlap scores of DomBpred are 0.523 and 0.824, respectively, which are 5.0% and 4.2% higher than those of the best comparison method, respectively. Comparison with other methods on the given test set shows that DomBpred outperforms most state-of-the-art sequence-based methods and even achieves better results than the top-level template-based method.
The effect of external stimulation on functional networks in the aging healthy human brain
Authors: Escrichs Anira , Perl Yonatan Sanz , Martínez-Molina Noelia , Biarnes Carles , Garre-Olmo Josep , Fernández-Real José Manuel , Ramos Rafel , Martí Ruth , Pamplona Reinald , Brugada Ramon , Serena Joaquin , Ramió-Torrentà Lluís , Coll-De-Tuero Gabriel , Gallart Luís , Barretina Jordi , Vilanova Joan C. , Mayneris-Perxachs Jordi , Saba Luca , Pedraza Salvador , Kringelbach Morten L. , Puig Josep , Deco Gustavo 
Published: November 2021

AbstractUnderstanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve as a more specific biomarker relating local activity with global brain dynamics. Here, we used a large resting-state fMRI dataset divided into middle-aged (N=310, aged < 65 years) and older adults (N=310, aged ≥ 65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space, each with a probabilistic occurrence and frequency. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations with different intensities in each node to force transitions from the brain states of the older group to the middle-age group. We found that the precuneus, a brain area belonging to the default mode network and the rich club, was the best stimulation target. These findings might have important implications for designing neurostimulation interventions to revert the effects of aging on whole-brain dynamics.
Model-checking ecological state-transition graphs
Authors: Thomas Colin , Cosme Maximilien , Gaucherel Cédric , Pommereau Franck 
Published: November 2021

AbstractModel-checking is a methodology developed in computer science to automatically assess the dynamics of discrete systems, by checking if a system modelled as a state-transition graph satisfies a dynamical property written as a temporal logic formula. The dynamics of ecosystems have been drawn as state-transition graphs for more than a century, from state-and-transition models to assembly graphs. Thus, model-checking can provide insights into both empirical data and theoretical models, as long as they sum up into state-transition graphs. While model-checking proved to be a valuable tool in systems biology, it remains largely underused in ecology. Here we promote the adoption of the model-checking toolbox in ecology through its application to an illustrative example. We assessed the dynamics of a vegetation model inspired from state-and-transition models by model-checking Computation Tree Logic formulas built from a proposed catalogue of patterns. Model-checking encompasses a wide range of concepts and available software, mentioned in discussion, thus its implementation can be fitted to the specific features of the described system. In addition to the automated analysis of ecological state-transition graphs, we believe that defining ecological concepts with temporal logics could help clarifying and comparing them.Author summaryEcologists have drawn state-transition graphs representing the dynamics of ecosystems for more than a century. Model-checking is an automated method for the analysis of such graphs developed in computer science and acknowledged by a Turing award in 2007. Ecologists appear to be mostly unaware of model-checking despite its successes in systems biology to assess the dynamics of biological networks.We promote model-checking of ecological state-transition graphs through its application to an illustrative vegetation model. We exemplify the insights provided by model-checking by assessing management policies aiming to tackle savanna encroachment. We also provide a catalogue of patterns to help ecologists with the difficulty of formally expressing dynamical properties. We also discuss the wide range of model-checking concepts and available software, enabling to fit the specific features of the studied system, such as durations or probabilities.Model-checking can be applied to both empirical data and theoretical models, as long as they sum up into state-transition graphs. It provides automated and accurate answers to complex questions that could barely be analysed through human examination, if not impossible to answer this way. In addition to the automated analysis of ecological state-transition graphs, we believe that formally defining ecological concepts within the model-checking framework could help in clarifying and comparing them.
DETIRE: A Hybrid Deep Learning Model for identifying Viral Sequences from Metagenomes
Authors: Miao Yan , Liu Fu , Hou Tao , Liu Qiaoliang , Dong Tian , Liu Yun 
Published: November 2021

AbstractA metagenome contains all DNA sequences from an environmental sample, including viruses, bacteria, fungi, actinomycetes and so on. Since viruses are of huge abundance and have caused vast mortality and morbidity to human society in history as a kind of major pathogens, detecting viruses from metagenomes plays a crucial role in analysing the viral component of samples and is the very first step for clinical diagnosis. However, detecting viral fragments directly from the metagenomes is still a tough issue because of the existence of huge number of short sequences. In this paper, a hybrid Deep lEarning model for idenTifying vIral sequences fRom mEtagenomes (DETIRE), is proposed to solve the problem. Firstly, the graph-based nucleotide sequence embedding strategy is utilized to enrich the expression of DNA sequences by training an embedding matrix. Then the spatial and sequential features are extracted by trained CNN and BiLSTM networks respectively to improve the feature expression of short sequences. Finally, the two set of features are weighted combined for the final decision. Trained by 220,000 sequences of 500bp subsampled from the Virus and Host RefSeq genomes, DETIRE identifies more short viral sequences (<1,000bp) than three latest methods, DeepVirFinder, PPR-Meta and CHEER. DETIRE is freely available athttps://github.com/crazyinter/DETIRE.
Simultaneous multicolor DNA-PAINT without sequential fluid exchange using spectral demixing
Authors: Gimber Niclas , Strauss Sebastian , Jungmann Ralf , Schmoranzer Jan 
Published: November 2021

ABSTRACTSeveral variants of multicolor single-molecule localization microscopy (SMLM) have been developed to resolve the spatial relationship of nanoscale structures in biological samples. The oligonucleotide-based SMLM approach ‘DNA-PAINT’ robustly achieves nanometer localization precision and can be used to count binding sites within nanostructures. However, multicolor DNA-PAINT has primarily been realized by ‘Exchange-PAINT’ that requires sequential exchange of the imaging solution and thus leads to extended acquisition times. To alleviate the need for fluid exchange and to speed up the acquisition of current multichannel DNA-PAINT, we here present a novel approach that combines DNA-PAINT with simultaneous multicolor acquisition using spectral demixing (SD). By using newly designed probes and a novel multichannel registration procedure we achieve simultaneous multicolor SD-DNA-PAINT with minimal crosstalk. We demonstrate high localization precision (3 – 6 nm) and multicolor registration of dual and triple-color SD-DNA-PAINT by resolving patterns on DNA origami nanostructures and cellular structures.
Oscillatory population-level activity of dorsal raphe serotonergic neurons sculpts sleep structure
Authors: Kato Tomonobu , Mitsukura Yasue , Yoshida Keitaro , Mimura Masaru , Takata Norio , Tanaka Kenji F. 
Published: November 2021

AbstractDorsal raphe (DR) 5-HT neurons are involved in regulating sleep-wake transitions. Previous studies demonstrated that single-unit activity of DR 5-HT neurons is high during wakefulness, decreases during non–rapid eye movement (NREM) sleep, and ceases during rapid eye movement (REM) sleep. However, characteristics of the population-level activity of DR 5-HT neurons, which can influence the entire brain, are largely unknown. Here we measured population activities of 5-HT neurons in male and female mouse DR across the sleep-wake cycle by a ratiometric fiber photometry system. We found a slow oscillatory activity of compound intracellular Ca2+ signals during NREM sleep. The trough of concave 5-HT activity increased along with sleep progression, but the 5-HT activity level always returned to that seen in wake periods. When the trough reached the minimum level and remained there, REM sleep initiated. We also found a unique coupling of the oscillatory 5-HT activity and EEG power fluctuation, suggesting that EEG fluctuation is a proxy for 5-HT activity. Optogenetic activation of 5-HT neurons during NREM sleep triggered a high EMG power and induced wakefulness. Optogenetic inhibition induced REM sleep or sustained NREM with an EEG power increase and EEG fluctuation. These manipulations demonstrated a causal role of DR 5-HT neurons in sculpting sleep-wake structure. We also observed EEG fluctuations in human males during NREM sleep, implicating the existence of 5- HT oscillatory activity in humans. We propose that NREM sleep is not a monotonous state, but that it is dynamically regulated by the oscillatory population activity of DR 5- HT neurons.Significant statementPrevious studies have demonstrated single-cell 5-HT neuronal activity across sleep- wake conditions; however, population-level activities of these neurons are largely unknown. We monitored dorsal raphe (DR) 5-HT population activity using a fiber photometry system in mice and demonstrated that activity was highest during wakefulness, and lowest during rapid eye movement (REM) sleep. Surprisingly, during non-REM (NREM) sleep, the 5-HT population activity decreased with an oscillatory pattern, coinciding with EEG fluctuations. We examined the causal role of these 5-HT neuron activities by optogenetics and found that DR 5-HT neurons sculpted sleep-wake conditions by influencing EEG and EMG patterns. We found similar EEG fluctuations in a human sleep EEG study, suggesting the presence of oscillatory 5-HT neuron activity during NREM across species.
A scalable analytical approach from bacterial genomes to epidemiology
Authors: Didelot Xavier , Parkhill Julian 
Published: November 2021

SummaryRecent years have seen a remarkable increase in the practicality of sequencing whole genomes from large numbers of bacterial isolates. The availability of this data has huge potential to deliver new insights into the evolution and epidemiology of bacterial pathogens, but the scalability of the analytical methodology has been lagging behind that of the sequencing technology. Here we present a step-by-step approach for such large-scale genomic epidemiology analyses, from bacterial genomes to epidemiological interpretations. A central component of this approach is the dated phylogeny, which is a phylogenetic tree with branch lengths measured in units of time. The construction of dated phylogenies from bacterial genomic data needs to account for the disruptive effect of recombination on phylogenetic relationships, and we describe how this can be achieved. Dated phylogenies can then be used to perform fine-scale or large-scale epidemiological analyses, depending on the proportion of cases for which genomes are available. A key feature of this approach is computational scalability, and in particular the ability to process hundreds or thousands of genomes within a matter of hours. This is a clear advantage of the step-by-step approach described here. We discuss other advantages and disadvantages of the approach, as well as potential improvements and avenues for future research.
A 1-bp deletion in bovineQRICH2causes low sperm count and immotile sperm with multiple morphological abnormalities
Authors: Hiltpold Maya , Janett Fredi , Mapel Xena Marie , Kadri Naveen Kumar , Fang Zih-Hua , Schwarzenbacher Hermann , Seefried Franz R , Spengeler Mirjam , Witschi Ulrich , Pausch Hubert 
Published: November 2021

AbstractBackgroundSemen quality and male fertility are monitored in artificial insemination bulls to ensure high insemination success rates. Only ejaculates that fulfill minimum quality requirements are processed and eventually used for artificial inseminations. We examined 70,990 ejaculates from 1343 Brown Swiss bulls to identify bulls from which all ejaculates were rejected due to low semen quality. This procedure identified a bull that produced twelve ejaculates with an aberrantly low number of sperm (0.2±0.2 × 109sperm per ml) which were mostly immotile due to multiple morphological abnormalities.ResultsThe genome of the bull was sequenced at 12-fold coverage to investigate a suspected genetic cause. Comparing the sequence variant genotypes of the bull with those from 397 fertile bulls revealed a 1-bp deletion in the coding sequence ofQRICH2encoding glutamine rich 2 as a compelling candidate causal variant. The 1-bp deletion causes a frameshift in translation and induces a premature termination codon (ENSBTAP00000018337.1:p.Cys1644AlafsTer52). The analysis of testis transcriptomes from 76 bulls showed that the transcript with the premature termination codon is subjected to nonsense-mediated mRNA decay. The 1-bp deletion resides on a 675 kb haplotype spanning 181 SNPs from the Illumina BovineHD Bead chip. The haplotype segregates at a frequency of 5% in the Brown Swiss cattle population. This analysis also identified another bull that carried the 1-bp deletion in the homozygous state. Semen analyses from the second bull confirmed low sperm concentration and immotile sperm with multiple morphological abnormalities primarily affecting the sperm flagellum and, to a lesser extent, the sperm head.ConclusionsA recessive loss-of-function allele of bovineQRICH2likely causes low sperm concentration and immotile sperm with multiple morphological abnormalities. Routine sperm analyses unambiguously identify homozygous bulls. A direct gene test can be implemented to monitor the frequency of the undesired allele in cattle populations.
Structural features within the NORAD long noncoding RNA underlie efficient repression of Pumilio activity
Authors: Ziv Omer , Farberov Svetlana , Lau Jian You , Miska Eric , Kudla Grzegorz , Ulitsky Igor 
Published: November 2021

AbstractIt is increasingly appreciated that long non-coding RNAs (lncRNAs) carry out important functions in mammalian cells, but how these are encoded in their sequences and manifested in their structures remains largely unknown. Some lncRNAs bind to and modulate the availability of RNA binding proteins, but the structural principles that underlie this mode of regulation are underexplored. Here, we focused on the NORAD lncRNA, which binds Pumilio proteins and modulates their ability to repress hundreds of mRNA targets. We probed the RNA structure and long-range RNA-RNA interactions formed by NORAD inside cells, under different stressful conditions. We discovered that NORAD structure is highly modular, and consists of well-defined domains that contribute independently to NORAD function. We discovered that NORAD structure spatially clusters the Pumilio binding sites along NORAD in a manner that contributes to the de-repression of Pumilio target proteins. Following arsenite stress, the majority of NORAD structure undergoes relaxation and forms inter-molecular interactions with RNAs that are targeted to stress granules. NORAD sequence thus dictates elaborated structural domain organization that facilitates its function on multiple levels, and which helps explain the extensive evolutionary sequence conservation of NORAD regions that are not predicted to directly bind Pumilio proteins.
Human macrophage polarization determines bacterial persistence ofStaphylococcus aureusin a liver-on-chip-based infection model
Authors: Siwczak Fatina , Cseresnyes Zoltan , Carlstedt Swen , Sigmund Anke , Gröger Marko , Surewaard Bas G.J. , Werz Oliver , Figge Marc Thilo , Tuchscherr Lorena , Löffler Bettina , Mosig Alexander S. 
Published: November 2021

AbstractInfections withStaphylococcus aureus(S. aureus) have been reported from various organs ranging from asymptomatic colonization to severe infections and sepsis associated with multiple organ dysfunction. Although considered an extracellular pathogen,S. aureuscan invade and persist in professional phagocytes such as monocytes and macrophages. Its capability to persist and manipulate phagocytes is considered a critical step to evade host antimicrobial reactions. For the first time we leveraged a human liver-on-chip model and tailored image analysis algorithms to demonstrate thatS. aureus(USA300) specifically targets macrophages in the liver models as essential niche facilitating bacterial persistence and phenotype switching to small colony variants (SCVs).In vitroM2 polarization was found to favor SCV-formation and was associated with increased intracellular bacterial loads in macrophages, increased cell death, and impaired recruitment of circulating monocytes to sites of infection. These findings expand the knowledge about the role of liver macrophages in the course of systemic infection. Further, the results might be relevant for understanding infection mechanisms in patients with chronic liver disease such as fibrosis that display increased frequencies of M2 polarized liver macrophages and have a higher risk for developing chronic infections and relapsing bacteremia.
Exploring genome gene content and morphological analysis to test recalcitrant nodes in the animal phylogeny
Authors: Juravel Ksenia , Porras Luis , Höhna Sebastian , Pisani Davide , Wörheide Gert 
Published: November 2021

AbstractAn accurate phylogeny of animals is needed to clarify their evolution, ecology, and impact on shaping the biosphere. Although datasets of several hundred thousand amino acids are nowadays routinely used to test phylogenetic hypotheses, key deep nodes in the metazoan tree remain unresolved: the root of animals, the root of Bilateria, and the monophyly of Deuterostomia. Instead of using the standard approach of amino acid datasets, we performed analyses of newly assembled genome gene content and morphological datasets to investigate these recalcitrant nodes in the phylogeny of animals. We explored extensively the choices for assembling the genome gene content dataset and model choices of morphological analyses. Our results are robust to these choices and provide additional insights into the early evolution of animals, they are consistent with sponges as the sister group of all the other animals, the worm-like bilaterian lineage Xenacoelomorpha as the sister group of the other Bilateria, and tentatively support monophyletic Deuterostomia.
STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia
Authors: Dinarello Alberto , Betto Riccardo Massimiliano , Diamante Linda , Cioccarelli Chiara , Meneghetti Giacomo , Peron Margherita , Tesoriere Annachiara , Laquatra Claudio , Tiso Natascia , Martello Graziano , Argenton Francesco 
Published: November 2021

ABSTRACTSTAT3 and HIF1α are two fundamental transcription factors involved in many merging processes, like angiogenesis, metabolism, and cell differentiation. Notably, under pathological conditions, the two factors have been shown to interact genetically, but both the molecular mechanisms underlying such interactions and their relevance under physiological conditions remain unclear. Here we report that STAT3 is required for the HIF1α-dependent response to hypoxia. In Stat3 knock-out pluripotent embryonic stem cells (ESCs), a large fraction of HIF1α target genes is not induced by hypoxia. Mechanistically, STAT3 does not regulate neither HIF1α expression nor stability, rather, it physically interacts with it in the nucleus. In vivo, we observed that both genetic and chemical inactivation of Stat3 blunted physiological responses to hypoxia, such as angiogenesis, erythropoiesis, and immune cell mobilization. Such defects were accompanied with faulty transcriptional activity of HIF1α. In sum, our data reveal that STAT3 and HIF1α cooperatively mediate the physiological response to hypoxia.
A chemerin peptide analog stimulates tumor growth in two xenograft mouse models of human colorectal carcinoma
Authors: Friebus-Kardash Justa , Schulz Petra , Reinicke Sandy , Karthaus Cordula , Schefer Quirino , Bandholtz Sebastian , Grötzinger Carsten 
Published: November 2021

AbstractBackgroundChemerin plasma concentration has been reported to be positively correlated with the risk of colorectal cancer. However, the potential regulation of CRC tumorigenesis and progression has not yet been investigated in an experimental setting. This study addresses this hypothesis by investigating proliferation, colony formation and migration of CRC cell lines in vitro as well as in animal models.MethodsIn vitro, microscopic assays to study proliferation as well as a scratch-wound assay for migration monitoring were applied using the human CRC cell lines HCT116, HT29 and SW620 under the influence of the chemerin analog CG34. The animal study investigated HCT116-luc and HT29-luc subcutaneous tumor size and bioluminescence during treatment with CG34 versus control, followed by ex-vivo analysis of vessel density and mitotic activity.ResultsWhile proliferation of the three CRC cell lines in monolayers was not clearly stimulated by CG34, the chemerin analog promoted colony formation in three-dimensional aggregates. An effect on cell migration was not observed. In the treatment study, CG34 significantly stimulated both growth and bioluminescence signal of HCT116-luc and HT29-luc xenografts.ConclusionsThe results of this study represent the first indication of a tumor growth-stimulating effect of chemerin signaling in CRC.