bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-GlcNAc regulates MTA1 transcriptional activity during breast cancer cells genotoxic adaptation
Authors: Xie Xueqin , Wu Qiutong , Zhang Keren , Liu Yimin , Zhang Nana , Chen Qiushi , Wang Lingyan , Li Wenli , Zhang Jianing , Liu Yubo 
Published: February 2021

AbstractChromatin modifier metastasis-associated protein 1 (MTA1), closely correlated with the development and progression in breast cancer, has a vital role in multiple cellular processes, including gene expression and cell homeostasis. Although MTA1 is a stress-responsive gene, its role in genotoxic adaptation remains unexplored. The current study sought to investigate the role of MTA1 and its O-GlcNAc modification in breast cancer cells genotoxic adaptation by using quantitative proteomics, ChIP-seq, transcriptome analysis, loss-and gain-of-functions experiments. We demonstrate that O-GlcNAc modification promotes MTA1 to interact with chromatin and regulates target gene expression, contributing to breast cancer cell genotoxic adaptation. MTA1 is modified with O-GlcNAc residues at serine 237/241/246 in adriamycin adaptive breast cancer cells and that modification improves the genome-wide interactions of MTA1 with gene promotor regions by enhancing its association with nucleosome remodeling and histone deacetylation (NuRD) complex. Further, O-GlcNAc-modulated MTA1 chromatin-binding influences the specific transcriptional regulation of genes involved in the adaptation of breast cancer cells to genotoxic stress. Our findings reveal a previously unrecognized role of O-GlcNAc MTA1 in transcriptional regulation and suggest that O-GlcNAc modification is a promising therapeutic target to overcome chemoresistance in breast cancers.
Cover crop residue diversity enhances microbial activity and biomass with additive effects on microbial structure
Authors: Shu Xin , Zou Yiran , Shaw Liz J. , Todman Lindsay , Tibbett Mark , Sizmur Tom 
Published: February 2021

AbstractCover crops have been widely used in agroecosystems to improve soil fertility and environmental sustainability. The decomposition of cover crop residues can have further effects on belowground communities and their activity, which is important for a series of soil functions (e.g., nutrient cycling and organic matter decomposition). We tested the effect of plant residues from a range of cover crop species on soil microbial activity and community assemblage. We predicted that cover crop residues would alter the soil microbial community and that a greater diversity of residues would enhance microbial decomposition. In an incubation study, we assessed the effect of crop residue diversity on microbial activity (soil respiration) and its consequent effects on microbial community composition (PLFA). We used either a biodiverse mixture of four cover crop residues (buckwheat, clover, sunflower and radish) or an equal mass of the residues of each of the individual species. The diverse mixture of cover crop residues had a significantly (P< 0.05) greater soil respiration rate, by 57.61 µg C g−1h−1, than the average of the four individual residues, but did not have a significantly different soil microbial biomass or microbial community structure. This finding could be attributed to a greater diversity of organic resources increasing the number biochemical niches, and hence activating dormant microbial communities to increase microbial activity without affecting microbial biomass or community composition. Greater respiration from similar microbial biomasses suggests that microbial activity might be more efficient after a more diverse substrate input. This study confirms the positive impact of cover crop residues on soil microbial biomass and activity and highlights that mixtures of cover crop residues may deliver enhanced soil functions beyond the sum of individual cover crop residues.
Rare long-range cortical connections enhance information processing
Authors: Deco Gustavo , Perl Yonathan Sanz , Vuust Peter , Tagliazucchi Enzo , Kennedy Henry , Kringelbach Morten L. 
Published: February 2021

SummaryWhat are the key topological features of connectivity critically relevant for generating the dynamics underlying efficient cortical function? A candidate feature that has recently emerged is that the connectivity of the mammalian cortex follows an exponential distance rule, which includes a small proportion of long-range high-weight anatomical exceptions to this rule. Whole-brain modelling of large-scale human neuroimaging data in 1003 participants offers the unique opportunity to create two models with and without long-range exceptions and explicitly study their functional consequences. We found that rare long-range exceptions are crucial for significantly improving information processing. Furthermore, modelling in a simplified ring architecture shows that this improvement is greatly enhanced by the turbulent regime found in empirical neuroimaging data. Overall, the results provide strong empirical evidence for the immense functional benefits of long-range exceptions combined with turbulence for information processing.
Sensory experience modulates the reorganisation of temporal auditory regions for executive processing
Authors: Manini Barbara , Vinogradova Valeria , Woll Bencie , Cameron Donnie , Eimer Martin , Cardin Velia 
Published: February 2021

AbstractCrossmodal plasticity refers to the reorganisation of sensory cortices in the absence of their main sensory input. Understanding this phenomenon provides insights into brain function and its potential for change and enhancement. Using fMRI, we investigated how early deafness influences crossmodal plasticity and the organisation of executive functions in the adult human brain. Results from a range of visual executive function tasks (working memory, task switching, planning, inhibition) show that deaf individuals specifically recruit “auditory” regions during task switching. Neural activity in superior temporal regions, most significantly in the right hemisphere, are good predictors of behavioural performance during task switching in the deaf group, highlighting the functional relevance of the observed cortical reorganisation. Our results show executive processing in typically sensory regions, suggesting that the development and ultimate role of brain regions are influenced by perceptual environmental experience.
Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency
Authors: Haswell Jeffrey R. , Mattioli Kaia , Gerhardinger Chiara , Maass Philipp G. , Foster Daniel J. , Fernandez Paola P. , Wang Xiaofeng , Rinn John L. , Slack Frank J. 
Published: February 2021

ABSTRACTAlthough many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we developed a clustering approach to infer mechanisms of action of lncRNA hits based on a variety of genomic features. We subsequently identified and validated FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and methodology described herein can be adapted to discover and characterize novel regulators of differentiation into any lineage.
Molecular Mechanism of Capsid Disassembly in Hepatitis B Virus
Authors: Ghaemi Zhaleh , Gruebele Martin , Tajkhorshid Emad 
Published: February 2021

AbstractThe disassembly of a viral capsid leading to the release of its genetic material into the host cell is a fundamental step in viral infection. Hepatitis B virus (HBV) in particular consists of identical capsid protein monomers that dimerize and also arrange themselves into pentamers or hexamers on the capsid surface. By applying atomistic molecular dynamics simulation to an entire solvated HBV capsid subject to a uniform mechanical stress protocol, we monitor the disassembly process down to the level of individual amino acids. The strain of an external force combined with thermal fluctuations causes structurally heterogeneous cracks to appear in the HBV capsid. Unlike the expectation from purely mechanical considerations, the cracks mainly occur within and between hexameric sites, whereas pentameric sites remain largely intact. Only a small subset of the capsid protein monomers governs disassembly. These monomers are distributed across the whole capsid, but belong to regions with a high degree of collective motion that we label ‘communities’. Cross-talk within these communities is a mechanism of crack propagation leading to destabilization of the entire capsid, and eventually its disassembly. We identify specific residues whose interactions are most readily lost during disassembly: R127, I139, Y132, N136, A137, and V149 are among the hotspots at the interfaces between dimers that lie within or span hexamers, leading to dissociation. The majority of these hotspots are evolutionary conserved, indicating that they are important for disassembly by avoiding over-stabilization of capsids.SignificanceHepatitis B virus (HBV) is a DNA virus that is 100 times more infectious than HIV. Despite the availability of a vaccine, the chronic infection rate of this virus is still about 300 million people globally. HBV chronic infection, for which no cure is currently available, can lead to liver cancer. Therefore, there is an unmet need to investigate the infection cycle of the virus. One of the most crucial steps in virus replication cycle is the release of its genetic material to the nucleus. During this step, the viral capsid enclosing the genetic material disassembles. However, its mechanism is unknown. Here, we utilize molecular simulations to shed light on the events leading to the capsid disassembly with atomistic detail.
Genetic models of latent tuberculosis in mice reveal differential control by adaptive immunity
Authors: Su Hongwei , Lin Kan , Tiwari Divya , Healy Claire , Trujillo Carolina , Liu Yao , Ioerger Thomas R. , Schnappinger Dirk , Ehrt Sabine 
Published: February 2021

AbstractStudying latentMycobacterium tuberculosis(Mtb) infection has been limited by the lack of a suitable mouse model. We discovered that transient depletion of protein biotin ligase (BPL) and thioredoxin reductase (TrxB2) results in latent infections during which Mtb cannot be detected but that relapse in a subset of mice. The immune requirements for Mtb control during latency, and the frequency of relapse, were strikingly different depending on how latency was established. TrxB2 depletion resulted in a latent infection that required adaptive immunity for control and reactivated with high frequency, whereas latent infection after BPL depletion was independent of adaptive immunity and rarely reactivated. We identified immune signatures of T cells indicative of relapse and demonstrated that BCG vaccination failed to protect mice from TB relapse. These reproducible genetic latency models allow investigating the host immunological determinants that control the latent state and offer opportunities to evaluate therapeutic strategies in settings that mimic aspects of latency and TB relapse in humans.
Structure and inhibitor binding characterization of oncogenic MLLT1 mutants
Authors: Ni Xiaomin , Londregan Allyn T. , Owen Dafydd R. , Knapp Stefan , Chaikuad Apirat 
Published: February 2021

AbstractDysfunction of YEATS-domain-containing MLLT1, an acetyl/acyl-lysine dependent epigenetic reader domain, has been implicated in the development of aggressive cancers. Mutations in the YEATS domain have been recently reported as a cause of MLLT1 aberrant reader function. However, structural basis for the reported alterations in affinity for acetyled/acylated histone has remained elusive. Here, we report the crystal structures of both insertion and substitution present in cancer, revealing significant conformational changes of the YEATS-domain loop 8. Structural comparison demonstrates that such alteration not only altered the binding interface for acetylated/acylated histones, but the sequence alterations in the T1 loop may enable dimeric assembly consistent inducing self-association behavior. Nevertheless, we show that also the MLLT1 mutants can be targeted by developed acetyllysine mimetic inhibitors with affinities similarly to wild type. Our report provides a structural basis for the altered behaviors and potential strategy for targeting oncogenic MLLT1 mutants.
Tacc3 modulates microtubule network dynamicity and focal adhesion remodeling to affect cranial neural crest cell migration inXenopus laevis
Authors: Bearce Elizabeth A. , Pratt Benjamin , Rutherford Erin , Carandang Leslie , Lowery Laura Anne 
Published: February 2021

AbstractCoordinated cell migration is critical during embryogenesis, as cells must leave their point of origin, navigate a complex barrage of signals, and accurately position themselves to facilitate correct tissue and organ formation. The cell motility process relies on dynamic interactions of the F-actin and microtubule (MT) cytoskeletons. Our work focuses on how one MT plus-end regulator, Transforming Acidic Coiled-Coil 3 (Tacc3), can impact migration of cranial neural crest cells inXenopus laevis. We previously demonstrated thattacc3expression is expressed in cranial neural crest cells, and that Tacc3 can function as a MT plus-end tracking protein to regulate MT growth velocities. Here, we demonstrate that manipulation of Tacc3 protein levels is sufficient to alter cranial neural crest cell velocityin vitro. Tacc3 overexpression drives increased single-cell migration velocities, while Tacc3 KD results in reduced cell velocity and defective explant dispersion. We also show that Tacc3 can have spatially-enhanced effects on MT plus-end growth velocities as well as effects on focal adhesion remodeling. Together, we demonstrate that Tacc3 can facilitate neural crest cell motility through spatially-enhanced cytoskeletal remodeling, which may underlie the enhanced metastatic potential of Tacc3-overexpressing tumor cells.
Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay
Authors: Cairrao Fatima , Santos Cristiana C , Le Thomas Adrien , Marsters Scot , Ashkenazi Avi , Domingos Pedro M. 
Published: February 2021

SUMMARYThe unfolded protein response (UPR) maintains homeostasis of the endoplasmic reticulum(ER). Residing in the ER membrane, the UPR mediator Ire1 deploys its cytoplasmic kinase-endoribonuclease domain to activate the key UPR transcription factor Xbp1 through non-conventional splicing of Xbp1 mRNA. Ire1 also degrades diverse ER-targeted mRNAs through regulated Ire1-dependent decay (RIDD), but how it spares Xbp1 mRNA from this decay is unknown. We identified binding sites for the RNA-binding protein Pumilio in the 3’UTRDrosophilaXbp1. In the developingDrosophila eye, Pumilio bound both the Xbp1unsplicedand Xbp1splicedmRNAs, but only Xbp1splicedwas stabilized by Pumilio. Furthermore, Pumilio displayed Ire1 kinase-dependent phosphorylation during ER stress, which was required for its stabilization of Xbp1spliced. Human IRE1 could directly phosphorylate Pumilio, and phosphorylated Pumilio protected Xbp1splicedmRNA against RIDD. Thus, Ire1-mediated phosphorylation enables Pumilio to shield Xbp1splicedfrom RIDD. These results uncover an important and unexpected regulatory link between an RNA-binding protein and the UPR.
Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse
Authors: Kallenbach Jacob G. , Freeberg Margaret A. T. , Abplanalp David , Myers Jacquelyn A. , Ashton John M. , Loiselle Alayna , Buckley Mark R. , van Wijnen Andre J. , Awad Hani A. 
Published: February 2021

AbstractTo better understand the molecular mechanisms of tendon healing, we investigated the Murphy Roth’s Large (MRL) mouse, which is considered a model of mammalian tissue regeneration. We show that compared to C57Bl/6J (C57) mice, injured MRL tendons have reduced fibrotic adhesions and cellular proliferation, with accelerated improvements in biomechanical properties. Transcriptional analysis of biological drivers showed positive enrichment of TGFB1 in both C57 and MRL healing tendons. However, only MRL tendons exhibited downstream transcriptional effects of cell cycle regulatory genes, with negative enrichment of the cell senescence-related regulators, compared to the positively-enriched inflammatory and ECM organization pathways in the C57 tendons. Serum cytokine analysis revealed decreased levels of circulating senescence-associated circulatory proteins (SASP) in response to injury in the MRL mice compared to the C57 mice. These data collectively demonstrate altered TGFB1 regulated inflammatory, fibrosis, and cell cycle pathways in flexor tendon repair.
Structure of the human SAGA coactivator complex: The divergent architecture of human SAGA allows modular coordination of transcription activation and co-transcriptional splicing
Authors: Herbst Dominik A. , Esbin Meagan N. , Louder Robert K. , Dugast-Darzacq Claire , Dailey Gina M. , Fang Qianglin , Darzacq Xavier , Tjian Robert , Nogales Eva 
Published: February 2021

AbstractHuman SAGA is an essential co-activator complex that regulates gene expression by interacting with enhancer-bound activators, recruiting transcriptional machinery, and modifying chromatin near promoters. Subunit variations and the metazoan-specific requirement of SAGA in development hinted at unique structural features of the human complex. Our 2.9 Å structure of human SAGA reveals intertwined functional modules flexibly connected to a core that distinctively integrates mammalian paralogs, incorporates U2 splicing subunits, and features a unique interface between the core and the activator-binding TRRAP. Our structure sheds light on unique roles and regulation of human coactivators with implications for transcription and splicing that have relevance in genetic diseases and cancer.
Investigating receptor-mediated antibody transcytosis using Blood-Brain Barrier organoid arrays
Authors: Simonneau Claire , Duschmalé Martina , Gavrilov Alina , Brandenberg Nathalie , Hoehnel Sylke , Ceroni Camilla , Lassalle Evodie , Knoetgen Hendrik , Niewoehner Jens , Villaseñor Roberto 
Published: February 2021

AbstractBackgroundThe pathways that control protein transport across the Blood-Brain Barrier (BBB) remain poorly characterized. Despite great advances in recapitulating the human BBBin vitro, current models are not suitable for systematic analysis of the molecular mechanisms of antibody transport. The gaps in our mechanistic understanding of antibody transcytosis hinder new therapeutic delivery strategy development.MethodsWe applied a novel bioengineering approach to generate human BBB organoids by the self-assembly of astrocytes, pericytes and brain endothelial cells with unprecedented throughput and reproducibility using micro patterned hydrogels. We designed a semi-automated and scalable imaging assay to measure receptor-mediated transcytosis of antibodies. Finally, we developed a workflow to use CRISPR/Cas9 gene editing in BBB organoid arrays to knock out regulators of endocytosis specifically in brain endothelial cells in order to dissect the molecular mechanisms of receptor-mediated transcytosis.ResultsBBB organoid arrays allowed the simultaneous growth of more than 5000 homogenous organoids per individual experiment in a highly reproducible manner. BBB organoid arrays showed low permeability to macromolecules and prevented transport of human non-targeting antibodies. In contrast, a monovalent antibody targeting the human transferrin receptor underwent dose- and time-dependent transcytosis in organoids. Using CRISPR/Cas9 gene editing in BBB organoid arrays, we showed that clathrin, but not caveolin, is required for transferrin receptor-dependent transcytosis.ConclusionsHuman BBB organoid arrays are a robust high-throughput platform that can be used to discover new mechanisms of receptor-mediated antibody transcytosis. The implementation of this platform during early stages of drug discovery can accelerate the development of new brain delivery technologies.
Unfalsified control design using a generalized cost function for a quadrotor
Authors: Hokmabadi Azam , Khodabandeh Mahdi 
Published: February 2021

Purpose
The purpose of this paper is to design a controller for a quadrotor only by using input–output data without a need for the system model.

Design/methodology/approach
Tracking control for the quadrotor is considered by using unfalsified control, which is one of the most recent strategies of robust adaptive control. The main assumption in unfalsified control design is that there is no access to the system model. Also, ideal path tracking and controlling the quadrotor are been paid attention to in the presence of external disturbances and uncertainties. First, unfalsified control method is introduced which is a data-driven and model-free approach in the field of adaptive control. Next, model of the quadrotor and unfalsified control design for the quadrotor are presented. Second, design of a control bank consisting of four proportional integral derivative controllers and a sliding mode controller is carried out.

Findings
A particular innovation on an unfalsified control algorithm in this paper is use of a generalized cost function in the hysteresis switching algorithm to find the best controller.

Originality/value
Finally, the performance and robustness of the designed controllers are investigated by simulation studies in various operating conditions including reference trajectory changes, facing to wind disturbance, uncertainty of the system and changes in payload, which show acceptable performances.
Hydrogen as the futuristic fuel for the aviation and aerospace industry – review
Authors: Gunasekar P. , Manigandan S. , T.R. Praveen Kumar 
Published: February 2021

Purpose
The rise in demand and high utilization of fuel causes severe environmental threat for the nations on the globe. Rapid burning potential of hydrogen produces enormous amount of thrust, and it is mainly owing to wide flame range and less onset of ignition.

Design/methodology/approach
The significant contribution of hydrogen as fuel has been explored by several researchers around the globe recently to use in aviation sector owing to its eco-friendly nature. Hydrogen is a safe and clean fuel, and it can be generated from several sources. The effects of addition on hydrogen on gas turbine on combustion characteristics and emission concentration level on atmosphere have been reviewed in this paper.

Findings
Incorporation of hydrogen is effective reducing nitrous oxide emission, high calorific value and flame less combustion. Addition of hydrogen to higher proportions enhances the combustion performance, minimizing the setbacks of conventional fuel and meets the specified standards on emission.

Originality/value
From the literature review, the comparative study on hydrogen with other fuel is explained. This paper concludes that addition of hydrogen in fuel enhances the performance of combustion on gas turbine engine along with significant reduction in emission levels.