bluuebunny/crossref_metadata_2025_split huggingface dataset:
slimr: An R package for integrating data and tailor-made population genomic simulations over space and time
Authors: Dinnage Russell , Sarre Stephen D. , Duncan Richard P. , Dickman Christopher R. , Edwards Scott V. , Greenville Aaron , Wardle Glenda , Gruber Bernd 
Published: August 2021

AbstractSoftware for realistically simulating complex population genomic processes is revolutionizing our understanding of evolutionary processes, and providing novel opportunities for integrating empirical data with simulations. However, the integration between simulation software and software designed for working with empirical data is currently not well developed. Here we present slimr, an R package designed to create a seamless link between standalone software SLiM 3.0, one of the most powerful population genomic simulation frameworks, and the R development environment, with its powerful data manipulation and analysis tools. We show how slimr facilitates smooth integration between genetic data, ecological data and simulation in a single environment. The package enables pipelines that begin with data reading, cleaning, and manipulation, proceed to constructing empirically-based parameters and initial conditions for simulations, then to running numerical simulations, and finally to retrieving simulation results in a format suitable for comparisons with empirical data – aided by advanced analysis and visualization tools provided by R. We demonstrate the use of slimr with an example from our own work on the landscape population genomics of desert mammals, highlighting the advantage of having a single integrated tool for both data analysis and simulation. slimr makes the powerful simulation ability of SliM 3.0 directly accessible to R users, allowing integrated simulation projects that incorporate empirical data without the need to switch between software environments. This should provide more opportunities for evolutionary biologists and ecologists to use realistic simulations to better understand the interplay between ecological and evolutionary processes.
Microalgal protein AstaP is a potent carotenoid solubilizer and delivery module with a broad carotenoid binding repertoire
Authors: Slonimskiy Yury B. , Egorkin Nikita A. , Friedrich Thomas , Maksimov Eugene G. , Sluchanko Nikolai N. 
Published: August 2021

AbstractCarotenoids are lipophilic substances with many biological functions, from coloration to photoprotection. Being potent antioxidants, carotenoids have multiple biomedical applications, including the treatment of neurodegenerative disorders and retina degeneration. Nevertheless, the delivery of carotenoids is substantially limited by their poor solubility in the aqueous phase. Natural water-soluble carotenoproteins can facilitate this task, necessitating studies on their ability to uptake and deliver carotenoids. One such promising carotenoprotein, AstaP (Astaxanthin-binding protein), was recently identified in eukaryotic microalgae, but its structure and functional properties remained largely uncharacterized. By using a correctly folded recombinant protein, here we show that AstaP is an efficient carotenoid solubilizer that can stably bind not only astaxanthin but also zeaxanthin, canthaxanthin, and, to a lesser extent, β-carotene, i.e. carotenoids especially valuable to human health. AstaP accepts carotenoids provided as acetone solutions or embedded in membranes, forming carotenoid-protein complexes with an apparent stoichiometry of 1:1. We successfully produced AstaP holoproteins in specific carotenoid-producing strains ofEscherichia coli, proving it is amenable to cost-efficient biotechnology processes. Regardless of the carotenoid type, AstaP remains monomeric in both apo- and holoforms, while its rather minimalistic mass (∼20 kDa) makes it an especially attractive antioxidant delivery module.In vitro, AstaP transfers different carotenoids to the liposomes and to unrelated proteins from cyanobacteria, which can modulate their photoactivity and/or oligomerization. These findings expand the toolkit of the characterized carotenoid-binding proteins and outline the perspective of the use of AstaP as a unique monomeric antioxidant nanocarrier with an extensive carotenoid-binding repertoire.
Contextual expectations shape cortical reinstatement of sensory representations
Authors: Clarke Alex , Crivelli-Decker Jordan , Ranganath Charan 
Published: August 2021

AbstractWhen making a turn at a familiar intersection, we know what items and landmarks will come into view. These perceptual expectations, or predictions, come from our knowledge of the context, however it’s unclear how memory and perceptual systems interact to support the prediction and reactivation of sensory details in cortex. To address this, human participants learned the spatial layout of animals positioned in a cross maze. During fMRI, participants navigated between animals to reach a target, and in the process saw a predictable sequence of five animal images. Critically, to isolate activity patterns related to item predictions, rather than bottom-up inputs, one quarter of trials ended early, with a blank screen presented instead. Using multivariate pattern similarity analysis, we reveal that activity patterns in early visual cortex, posterior medial regions, and the posterior hippocampus showed greater similarity when seeing the same item compared to different items. Further, item effects in posterior hippocampus were specific to the sequence context. Critically, activity patterns associated with seeing an item in visual cortex and posterior medial cortex, were also related to activity patterns when an item was expected, but omitted, suggesting sequence predictions were reinstated in these regions. Finally, multivariate connectivity showed that patterns in the posterior hippocampus at one position in the sequence were related to patterns in early visual cortex and posterior medial cortex at a later position. Together, our results support the idea that hippocampal representations facilitate sensory processing by modulating visual cortical activity in anticipation of expected items.
Histone H3K36me2-specific methyltransferase ASH1L is required for the MLL-AF9-induced leukemogenesis
Authors: Aljazi Mohammad B. , Gao Yuen , Wu Yan , Mias George I , He Jin 
Published: August 2021

AbstractASH1L and MLL1 are two histone methyltransferases that facilitate transcriptional activation during normal development. However, the roles of ASH1L and its enzymatic activity in the development of MLL-rearranged leukemias are not fully elucidated in the Ash1L gene knockout animal models. In this study, we used an Ash1L conditional knockout mouse model to show that loss of ASH1L in hematopoietic progenitor cells impaired the initiation of MLL-AF9-induced leukemic transformation in vitro. Furthermore, genetic deletion of ASH1L in the MLL-AF9-transformed cells impaired the maintenance of leukemic cells in vitro and largely blocked the leukemia progression in vivo. Importantly, the loss of ASH1L function in the Ash1L-deleted cells could be rescued by wild-type but not the catalytic-dead mutant ASH1L, suggesting the enzymatic activity of ASH1L was required for its function in promoting MLL-AF9-induced leukemic transformation. At the molecular level, ASH1L enhanced the MLL-AF9 target gene expression by directly binding to the gene promoters and modifying the local histone H3K36me2 levels. Thus, our study revealed the critical functions of ASH1L in promoting the MLL-AF9-induced leukemogenesis, which provides a molecular basis for targeting ASH1L and its enzymatic activity to treat MLL-arranged leukemias.
Developing a Novel Positronium Biomarker for Cardiac Myxoma Imaging
Authors: Moskal Paweł , Kubicz Ewelina , Grudzień Grzegorz , Czerwiński Eryk , Dulski Kamil , Leszczyński Bartosz , Niedźwiecki Szymon , Stępień Ewa Ł. 
Published: August 2021

AbstractHere, positronium imaging is presented to determine cardiac myxoma (CM) extracted from patients undergoing urgent cardiac surgery due to unexpected atrial masses. Positronium is an atom build from an electron and a positron, produced copiously in intra-molecular voids during the PET imaging. CM, the most common cardiac tumor in adults, accounts for 50-75% of benign cardiac tumors. We aimed to assess if positronium serves as a biomarker for diagnosing CM. Perioperative examinations and histopathology staining in six patients confirmed the primary diagnosis of CM. We observed significant differences in the mean positronium lifetime between tumor and normal tissues, with an average value of 1.92(02) ns and 2.72(05) ns for CM and the adipose tissue, respectively. Our findings, combined with positronium lifetime imaging, reveals the novel emerging positronium biomarker for cardiovascular imaging.One-Sentence SummaryPositronium may serve as an imaging biomarker for cancer diagnostics.
MotSASi: Functional Short Linear Motifs (SLiMs) prediction based on genomic single nucleotide variants and structural data
Authors: Martín Mariano , Modenutti Carlos P. , Nicola Juan P. , Marti Marcelo A. 
Published: August 2021

AbstractShort linear motifs (SLiMs) are key to cell physiology mediating reversible protein-protein interactions. Precise identification of SLiMs remains a challenge, being the main drawback of most bioinformatic prediction tools their low specificity (high number of false positives). An important, usually overlooked, aspect is the relation between SLiMs mutations and disease. The presence of variants in each residue position can be used to assess the relevance of the corresponding residue(s) for protein function, and its (in)tolerance to change.In the present work, we combined sequence variant information and structural analysis of the energetic impact of single amino acid substitution (SAS) in SLiM-Receptor complex structure, and showed that it significantly improves prediction of true functional SLiMs. Our strategy is based on building a SAS tolerance matrix that shows, for each position, whether one of the possible 19 SAS is tolerated or not. Herein we present the MotSASi strategy and analyze in detail 4 SLiMs involved in intracellular protein trafficking. Our results show that inclusion of variant and sequence information significantly improves both prediction of true SLiMs and rejection of false positives, while also allowing better classification of variants inside SLiMs, a results with a direct impact in clinical genomics.
Inhibitory effect of an anti-prokineticin-1 antibody on liver metastases in mice injected with human colorectal cancer cell lines
Authors: Kono Hiroko , Goi Takanori , Kurebayashi Hidetaka , Sawai Katsuji , Morikawa Mitsuhiro , Koneri Kenji 
Published: August 2021

AbstractControlling hematogenous metastases is an effective treatment strategy for colorectal cancer. Multidisciplinary treatment for colorectal cancer has made great strides, and molecularly-targeted drugs have greatly improved the prognosis of patients. However, currently accepted molecularly- targeted therapeutic agents require concomitant use with anticancer agents. Thus, new molecularly-targeted drugs need to be developed. The prokineticin family of angiogenic factors has the potential of becoming target molecules. Among them, prokineticin-1 (PROK1) is involved in the promotion of angiogenesis, tumor growth, and liver metastases in colorectal cancer. We manufactured our own anti-PROK1 antibody and verified its effect in inhibiting liver metastases and prolonging survival. The method involved creating liver metastasis model mice using human colorectal cancer cell lines. These mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every 3 days. The number of liver metastatic lesions and survival time of each group were compared. The number of metastatic lesions decreased, and survival time was significantly prolonged in the antibody-treated group. Furthermore, using microarray and immunostaining in both groups, we confirmed the effect of administering the anti-PROK1 antibody on the oxidation, reduction, and apoptotic processes, and cell division of tumors, and that alterations were suppressed in 72.1% of the genes examined. The expression of transforming growth factor-β (TGF-β), a tumor suppressor gene, was increased. The increased expression of TGF-β via PROK1 antibody administration may suppress the cancer cell proliferation ability, leading to liver metastasis suppression and prolonging the survival time of mice.
Pollen meta-barcoding reveals foraging preferences of honeybees (Apis melliferaL.) along space-time gradient in Japan
Authors: Noël Grégoire , Mestrez Arnaud , Lejeune Philippe , Francis Frédéric , Miwa Masayuki , Uehara Koichi , Nagase Ayako 
Published: August 2021

AbstractThe availability of pollen in urban-rural landscapes is an essential factor that influences the population dynamics of insect pollinators. The amount and diversity of pollen play a pivotal role in the foraging ecology of pollinators for their growth and health, but investigations on the spatio-temporal patterns of foraged plants remain rare, especially in cities as neo-ecosystems. Here, we explored the temporal foraging habits of a highly polylectic pollinator (Apis melliferaL.) in a study area, including different landscape classes from rural to urban areas. Mixed-pollen in each month and each location (N = 17) were analysed using DNA meta-barcoding to identify plants visited by honeybees. The results showed that the landscape class (rural, suburban and urban areas) explains spatial variations in the plant composition foraged by honeybees, but not in taxa richness. Furthermore, pollen diversity and plant composition showed a strong seasonal dependence. Furthermore, a higher plant richness and foraged woody taxa was found to occur in spring, which was mainly dominated by the generaPrunusandAcer. In summer and autumn, the generaTrifoliumandPlantagoof the herbaceous stratum were the most visited plants. The Fabaceae, Rosaceae, Brassicaceae, Plantaginaceae, and Onagraceae plant families were the most frequently observed in all combined samples. The present study contributes to a broader understanding of the ecology and floral preferences of honeybees, on which urban planning can rely to promote biodiversity in cities.
Microarray Analysis of Potential Biomarkers for brachial plexus avulsion caused neuropathic pain
Authors: Wang Le , Lao Jie 
Published: August 2021

AbstractNerve injury-induced neuropathic pain remains a challenging clinical problem due to a lack of satisfactory treatment. Pain after BPA (Brachial Plexus Avulsion) is resistant to most traditional pain relief treatments due to the lack of understanding of the cellular or molecular mechanism of pain development. The present study aimed to investigate the expression of mRNA in the brachial plexus avulsion neuropathic pain model and analyze biological functions. Sprague-Dawley rats were treated with complete brachial plexus avulsion. An animal behavior test was carried out to distinguish the pain group from the control group. In this study, a microarray mRNA assay and reverse transcriptase quantitative polymerase chain reaction (RT-PCR) was conducted. The whole blood was collected from two groups for Microarray mRNA analysis. The predicted mRNA targets were studied by gene ontology analysis and pathway analysis. The PIK3CB, HRAS, and JUN genes were verified by RT-PCR. In total, differentially expressed genes(DEGs) were identified between individuals with or without neuropathic pain (case and control), and A biological processes were enriched. We identified 3 targeted mRNAs, including PIK3CB, HRAS, and JUN, which may be potential biomarkers for BPA-caused NP. The results showed that PIK3CB, HRAS, and JUN gene expression was increased in the control group but decreased in the neuropathic pain group. The PIK3CB gene was part of the Neurotrophin signaling pathway. The function of the HRAS gene was synergetic in the aspect of axon guidance and the Neurotrophin signaling pathway. The JUN gene participates in axon regeneration. These results suggest that PIK3CB, HRAS, and JUN genes might become potential biomarkers for the prediction of and new targets for the prevention and treatment of neuropathic pain after BPA. These findings indicate that mRNA expression changes in the blood may play an important role in the development of NP after BPA, which is of theoretical and clinical importance for future research and clinical-treatment strategies.
Heterochromatin diversity modulates genome compartmentalization and loop extrusion barriers
Authors: Spracklin George , Abdennur Nezar , Imakaev Maxim , Chowdhury Neil , Pradhan Sriharsa , Mirny Leonid , Dekker Job 
Published: August 2021

AbstractTwo dominant processes organizing chromosomes are loop extrusion and the compartmental segregation of active and inactive chromatin. The molecular players involved in loop extrusion during interphase, cohesin and CTCF, have been extensively studied and experimentally validated. However, neither the molecular determinants nor the functional roles of compartmentalization are well understood. Here, we distinguish three inactive chromatin states using contact frequency profiling, comprising two types of heterochromatin and a previously uncharacterized inactive state exhibiting a neutral interaction preference. We find that heterochromatin marked by long continuous stretches of H3K9me3, HP1α and HP1β correlates with a conserved signature of strong compartmentalization and is abundant in HCT116 colon cancer cells. We demonstrate that disruption of DNA methyltransferase activity dramatically remodels genome compartmentalization as a consequence of the loss of H3K9me3 and HP1 binding. Interestingly, H3K9me3-HP1α/β is replaced by the neutral inactive state and retains late replication timing. Furthermore, we show that H3K9me3-HP1α/β heterochromatin is permissive to loop extrusion by cohesin but refractory to CTCF, explaining a paucity of visible loop extrusion-associated patterns in Hi-C. Accordingly, CTCF loop extrusion barriers are reactivated upon loss of H3K9me3-HP1α/β, not as a result of canonical demethylation of the CTCF binding motif but due to an intrinsic resistance of H3K9me3-HP1α/β heterochromatin to CTCF binding. Together, our work reveals a dynamic structural and organizational diversity of the inactive portion of the genome and establishes new connections between the regulation of chromatin state and chromosome organization, including an interplay between DNA methylation, compartmentalization and loop extrusion.HighlightsThree inactive chromatin states are distinguishable by long-range contact frequencies in HCT116, respectively associated with H3K9me3, H3K27me3 and a H3K9me2 state with neutral contact preferences.H3K9me3-HP1α/β heterochromatin has a high degree of homotypic affinity and is permissive to loop extrusion but depleted in extrusion barriers.Disrupting DNA methylation causes widespread loss of H3K9me3-HP1α/β and dramatic remodeling of genome compartmentalization.H3K9me3-HP1α/β is replaced by the neutral inactive state, which gains CTCF loop extrusion barriers and associated contact frequency patterns.DNA methylation suppresses CTCF binding via two distinct mechanisms.
The Inherent Flexibility of Receptor Binding Domains in SARS-CoV-2 Spike Protein
Authors: Dokainish Hisham M. , Re Suyong , Mori Takaharu , Kobayashi Chigusa , Jung Jaewoon , Sugita Yuji 
Published: August 2021

AbstractSpike (S) protein is the primary antigenic target for neutralization and vaccine development for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It decorates the virus surface and undergoes large conformational changes of its receptor binding domain (RBD) to enter the host cell, as the abundant structural studies suggest. Here, we observe Down, one-Up, one-Open, and two-Up-like structures in enhanced molecular dynamics simulations without pre-defined reaction coordinates. The RBDA transition from Down to one-Up is supported by transient salt-bridges between RBDA and RBDC and by the glycan at N343B. Reduced interactions between RBDA and RBDB induce the RBDB motions toward two-Up. Glycan shielding for neutralizing antibodies is the weakest in one-Open. Cryptic pockets are revealed at the RBD interfaces in intermediate structures between Down and one-Up. The inherent flexibility in S-protein is, thus, essential for the structure transition and shall be considered for antiviral drug rational design or vaccine development.
A study of Chinese college students' COVID-19-related information needs and seeking behavior
Authors: Huang Kun , Hao Xijia , Guo Miao , Deng Jingyuan , Li Lei 
Published: August 2021

PurposeTo better meet people's information needs under the public health crisis, this study explored the information needs and seeking behavior of college students in the context of the COVID-19 pandemic.Design/methodology/approachThis research utilized a survey and the convenience snowball sampling method. A sample of 400 college students was obtained.FindingsThe results revealed that college students have paid great attention to COVID-19-related information. They sought the information mainly for personal protection, obtaining the latest information and seeking information for family and friends. Their COVID-19-related information needs were diverse; at different stages, the concerns were different. Social media and mass media were both found to be the most useful tools for seeking COVID-19 information. Too much repetitive information, unclear authoritative and reliable informational sources, and difficulties in judging the authenticity of the information were the most common obstacles for them in information seeking. Nevertheless, the majority of the students agreed that they were very satisfied and somewhat satisfied with the current information services. This did not affect the students' understanding of the importance of health services provided by libraries.Originality/valueInsights into the people's information needs and information-seeking behavior of this study could help the information providers to offer appropriate information in better ways to improve the public's virus protection capabilities and maintain the stability of social order.