bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Reinforcement Meta-Learning Framework of Executive Function and Information Demand
Authors: Silvetti Massimo , Lasaponara Stefano , Horan Mattias , Gottlieb Jacqueline 
Published: July 2021

AbstractGathering information is crucial for maximizing fitness, but requires diverting resources from searching directly for primary rewards to actively exploring the environment. Optimal decision-making thus maximizes information while reducing effort costs, but little is known about the neural implementation of these tradeoffs. We present a Reinforcement Meta-Learning (RML) computational mechanism that solves the trade-offs between the value and costs of gathering information. We implement the RML in a biologically plausible architecture that links catecholaminergic neuromodulators, the medial prefrontal cortex and topographically organized visual maps and show that it accounts for neural and behavioral findings on information demand motivated by instrumental incentives and intrinsic utility. Moreover, the utility function used by the RML, encoded by dopamine, is an approximation of free-energy. Thus, the RML presents a biologically plausible mechanism through which coordinated motivational, executive and sensory systems generate visual information gathering policies that minimize free energy.
Experimental investigations of the human oesophagus: anisotropic properties of the muscular layer in large deformation
Authors: Durcan Ciara , Hossain Mokarram , Chagnon Grégory , Perić Djordje , Bsiesy Lara , Karam Georges , Girard Édouard 
Published: July 2021

AbstractTechnological advancements in the field of robotics have led to endoscopic biopsy devices able to extract diseased tissue from between the layers of the gastrointestinal tract. Despite this, the layer-dependent properties of these tissues have yet to be mechanically characterised using human tissue. In this study, the ex vivo mechanical properties of the passive muscularis propia layer of the human oesophagus were extensively investigated. For this, a series of uniaxial tensile tests were conducted. The results displayed hyperelastic behaviour, while the differences between loading the tissue in both the longitudinal and circumferential directions showcased its anisotropy. The anisotropy of the muscular layer was present at different strain rates, with the longitudinal direction being consistently stiffer than the circumferential one. The circumferential direction was found to have little strain-rate dependency, while the longitudinal direction results suggest pronounced strain-rate-dependent behaviour. The repeated trials showed larger variation in terms of stress for a given strain in the longitudinal direction compared to the circumferential direction. The possible causes of variation between trials are discussed, and the experimental findings are linked to the histological analysis which was carried out via various staining methods. Finally, the direction-dependent experimental data was simulated using an anisotropic, hyperelastic model.
Dynamic mechanisms of CRISPR interference by Escherichia coli CRISPR-Cas3
Authors: Yoshimi Kazuto , Takeshita Kohei , Kodera Noriyuki , Shibumura Satomi , Yamauchi Yuko , Omatsu Mine , Kunihiro Yayoi , Yamamoto Masaki , Mashimo Tomoji 
Published: July 2021

AbstractType I CRISPR-Cas3 uses an RNA-guided multi Cas-protein complex, Cascade, which detects and degrades foreign nucleic acids via the helicase-nuclease Cas3 protein. Despite many studies using cryoEM and smFRET, the precise mechanism of Cas3-mediated cleavage and degradation of target DNA remains elusive. Here we reconstitute the CRISPR-Cas3 system in vitro to show how the Escherichia coli Cas3 (EcoCas3) with EcoCascade exhibits collateral non-specific ssDNA cleavage and target specific DNA degradation. Partial binding of EcoCascade to target DNA with tolerated mismatches within the spacer sequence, but not the PAM, elicits collateral ssDNA cleavage activity of recruited EcoCas3. Conversely, stable binding with complete R-loop formation drives EcoCas3 to nick the non-target strand (NTS) in the bound DNA. Helicase-dependent unwinding then combines with trans ssDNA cleavage of the target strand and repetitive cis cleavage of the NTS to degrade the target dsDNA substrate. High-speed atomic force microscopy demonstrates that EcoCas3 bound to EcoCascade repeatedly reels and releases the target DNA, followed by target fragmentation. Together, these results provide a revised model for collateral ssDNA cleavage and target dsDNA degradation by CRISPR-Cas3, furthering understanding of type I CRISPR priming and interference and informing future genome editing tools.
Common molecular mechanisms underlie the transfer of alpha-synuclein, Tau and huntingtin and modulate spontaneous activity in neuronal cells
Authors: Brás Inês Caldeira , Khani Mohammad Hossein , Vasili Eftychia , Möbius Wiebke , Riedel Dietmar , Parfentev Iwan , Gerhardt Ellen , Fahlbusch Christiane , Urlaub Henning , Zweckstetter Markus , Gollisch Tim , Outeiro Tiago Fleming 
Published: July 2021

AbstractThe misfolding and accumulation of disease-related proteins are common hallmarks among several neurodegenerative diseases. Alpha-synuclein (aSyn), Tau and huntingtin (wild-type and mutant, 25QHtt and 103QHtt, respectively) were recently shown to be transferred from cell-to-cell through different cellular pathways, thereby contributing to disease progression and neurodegeneration. However, the relative contribution of each of these mechanisms towards the spreading of these different proteins and the overall effect on neuronal function is still unclear.To address this, we exploited different cell-based systems to conduct a systematic comparison of the mechanisms of release of aSyn, Tau and Htt, and evaluated the effects of each protein upon internalization in microglial, astrocytic, and neuronal cells. In the models used, we demonstrate that 25QHtt, aSyn and Tau are released to the extracellular space at higher levels than 103QHtt, and their release can be further augmented with the co-expression of USP19. Furthermore, cortical neurons treated with recombinant monomeric 43QHtt exhibited alterations in neuronal activity that correlated with the toxicity of the polyglutamine expansion. Tau internalization resulted in an increase in neuronal activity, in contrast to slight effects observed with aSyn. Interestingly, all these disease-associated proteins were present at higher levels in ectosomes than in exosomes. The internalization of both types of extracellular vesicles (EVs) by microglial or astrocytic cells elicited the production of pro-inflammatory cytokines and promoted an increase in autophagy markers. Additionally, the uptake of the EVs modulated neuronal activity in cortical neurons.Overall, our systematic study demonstrates the release of neurodegenerative disease-associated proteins through similar cellular pathways. Furthermore, it emphasizes that protein release, both in a free form or in EVs, might contribute to a variety of detrimental effects in receiving cells and to progression of pathology, suggesting they may be exploited as valid targets for therapeutic intervention in different neurodegenerative diseases.Graphical abstract
Susceptibilities of human ACE2 genetic variants in coronavirus infection
Authors: Ren Wenlin , Zhu Yunkai , Lan Jun , Chen Hedi , Wang Yuyan , Shi Hongyang , Feng Fei , Chen Da-Yuan , Close Brianna , Zhao Xiaomin , Wu Jianping , Tian Boxue , Yuan Zhenghong , Zhou Dongming , Saeed Mohsan , Wang Xinquan , Zhang Rong , Ding Qiang 
Published: July 2021

ABSTRACTThe COVID-19 pandemic, caused by SARS-CoV-2, has resulted in more than 1603 million cases worldwide and 3.4 million deaths (as of May 2021), with varying incidences and death rates among regions/ethnicities. Human genetic variation can affect disease progression and outcome, but little is known about genetic risk factors for SARS-CoV-2 infection. The coronaviruses SARS-CoV, SARS-CoV-2 and HCoV-NL63 all utilize the human protein angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells. We hypothesized that the genetic variability in ACE2 may contribute to the variable clinical outcomes of COVID-19. To test this hypothesis, we first conducted an in silico investigation of single-nucleotide polymorphisms (SNPs) in the coding region of ACE2 gene. We then applied an integrated approach of genetics, biochemistry and virology to explore the capacity of select ACE2 variants to bind coronavirus spike protein and mediate viral entry. We identified the ACE2 D355N variant that restricts the spike protein-ACE2 interaction and consequently limits infection both in vitro and in vivo. In conclusion, ACE2 polymorphisms could modulate susceptibility to SARS-CoV-2, which may lead to variable disease severity.
3D molecular phenotyping of cleared human brain tissues with light-sheet fluorescence microscopy
Authors: Pesce Luca , Scardigli Marina , Gavryusev Vladislav , Laurino Annunziatina , Mazzamuto Giacomo , Sancataldo Giuseppe , Silvestri Ludovico , Destrieux Christophe , Hof Patrick R. , Costantini Irene , Pavone Francesco S. 
Published: July 2021

AbstractThe combination of optical tissue transparency with immunofluorescence allows the molecular characterization of biological tissues in 3D. However, adult human organs are particularly challenging to become transparent because of the autofluorescence contributions of aged tissues. To meet this challenge, we optimized SHORT (SWITCH - H2O2 - antigen Retrieval - TDE), a procedure based on standard histological treatments in combination with a refined clearing procedure to clear and label portions of the human brain. 3D histological characterization with multiple molecules is performed on cleared samples with a combination of multi-colors and multi-rounds labeling. By performing fast 3D imaging of the samples with a custom-made inverted light-sheet fluorescence microscope (LSFM), we reveal fine details of intact human brain slabs at subcellular resolution. Overall, we proposed a scalable and versatile technology that in combination with LSFM allows mapping the cellular and molecular architecture of the human brain, paving the way to reconstruct the entire organ.
Towards on-chip real-time classification of extra-cellular neural recordings
Authors: Ozdas Mehmet , Gronskaya Elena , von der Behrens Wolfger , Indiveri Giacomo 
Published: July 2021

AbstractOn-line classification of neural recordings can be extremely useful in brain-machine interface, prosthetic applications or therapeutic intervention. In this work we present a feasibility study for developing compact low-power VLSI systems able to classify neural recordings in real-time, using spike-based neuromorphic circuits. We developed a framework for classifying extra-cellular recordings made in rat auditory cortex in response to different auditory stimuli and porting the classification algorithm onto a spiking multi-neuron VLSI chip with programmable synaptic weights. We present recording methods and software classification algorithms; we demonstrate real-time classification in hardware and quantify the system performance; finally, we identify the potential sources of problems in developing such types of systems and propose strategies for overcoming them.
Prior Signal Acquisition Software Versions for Orbitrap Underestimate Low Isobaric Mass Tag Intensities, Without Detriment to Differential Abundance Experiments
Authors: Smith Tom S , Andrejeva Anna , Christopher Josie A. , Crook Oliver M. , Elzek Mohamed A. W. , Lilley Kathryn S 
Published: July 2021

AbstractTandem mass tags (TMT) enable simple and accurate quantitative proteomics for multiplexed samples by relative quantification of tag reporter ions. Orbitrap™ quantification of reporter ions has been associated with a characteristic notch region in intensity distribution, within which few reporter intensities are recorded. This has been resolved in version 3 of the instrument acquisition software, Tune. However, 53 % of Orbitrap Fusion, Lumos or Eclipse submissions to PRIDE were generated using prior software versions. To quantify the impact of the notch on existing quantitative proteomics data, we generated a mixed species benchmark and acquired quantitative data using Tune versions 2 and 3. Sub-notch intensities are systemically underestimated with Tune version 2, leading to over-estimation of the true differences in intensities between samples. However, when summarising reporter ion intensities to higher level features, such as peptides and proteins, few features are significantly affected. Targeted removal of spectra with reporter ion intensities below the notch is not beneficial for differential peptide or protein testing. Overall, we find the systematic quantification bias associated with the notch is not detrimental for a typical proteomics experiment.
Ankyrin2 is required for neuronal morphogenesis and long-term memory and interacts genetically with HDAC4
Authors: Schwartz Silvia , Wilson Sarah J , Hale Tracy K , Fitzsimons Helen L 
Published: July 2021

AbstractDysregulation ofHDAC4expression and/or subcellular distribution results in impaired neuronal morphogenesis and long-term memory inDrosophila melanogaster. A recent genetic screen for genes that interact in the same molecular pathway asHDAC4identified the cytoskeletal adapterAnkyrin2(Ank2). Here we sought to investigate the role ofAnk2in neuronal morphogenesis, learning and memory, and to examine the nature of interaction withHDAC4. We found that Ank2 is expressed widely throughout theDrosophilabrain where it localizes predominantly to axon tracts. Pan-neuronal knockdown ofAnk2in the mushroom body, a region critical for memory formation, resulted in defects in axon morphogenesis, and similarly reduction ofAnk2in lobular plate tangential neurons of the optic lobe disrupted dendritic branching and arborization. Conditional knockdown ofAnk2in the mushroom body of adultDrosophilasignificantly impaired long-term courtship memory, and this requirement forAnk2was isolated to gamma (γ) neurons of the mushroom body. As overexpression ofHDAC4in γ neurons also impairs the formation of long-term courtship memory, this suggests that any functional relationship between these proteins during LTM likely occurs in γ neurons. We determined that the genetic interaction requires the presence of nuclearHDAC4and is not dependent on a conserved putative ankyrin-binding motif present in HDAC4. In summary, we provide the first characterization of the expression pattern of Ank2 in the adultDrosophilabrain and demonstrate that Ank2 is critical for morphogenesis of the mushroom body and for the molecular processes required in the adult brain for formation of long-term memories.
ACVR1 antibodies exacerbate heterotopic ossification in fibrodysplasia ossificans progressiva (FOP) by activating FOP-mutant ACVR1
Authors: Aykul Senem , Huang Lily , Wang Lili , Das Nanditha , Reisman Sandra , Ray Yonaton , Zhang Qian , Rothman Nyanza , Nannuru Kalyan C. , Kamat Vishal , Brydges Susannah , Troncone Luca , Johnsen Laura , Yu Paul B. , Fazio Sergio , Lees-Shepard John , Schutz Kevin , Murphy Andrew J. , Economides Aris N. , Idone Vincent , Hatsell Sarah J. 
Published: July 2021

AbstractFibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder whose most debilitating pathology is progressive and cumulative heterotopic ossification (HO) of skeletal muscles, ligaments, tendons, and fascia. FOP is caused by mutations in the type I BMP receptor gene ACVR1, which enable ACVR1 to utilize its natural antagonist, Activin A, as an agonistic ligand. The physiological relevance of this property is underscored by the fact that HO in FOP is exquisitely dependent on activation of FOP-mutant ACVR1 by Activin A, an effect countered by inhibition of Activin A via monoclonal antibody treatment. Hence, we surmised that ACVR1 antibodies that block activation of ACVR1 by ligand should also inhibit HO in FOP and provide an additional therapeutic option for this condition. Therefore, we generated ACVR1 monoclonal antibodies that block ACVR1’s activation by its ligands. Surprisingly, in vivo, these ACVR1 antibodies stimulate HO and activate signaling of FOP-mutant ACVR1. This property is restricted to FOP-mutant ACVR1 and results from ACVR1 antibody-mediated dimerization of ACVR1. Conversely, wild type ACVR1 is inhibited by ACVR1 antibodies. These results uncover an additional novel property of FOP-mutant ACVR1 and indicate that ACVR1 antibodies should not be considered as therapeutics for FOP.
Evolution of Plant Niche Construction Traits in Biogeomorphic Landscapes
Authors: Dong Xiaoli 
Published: July 2021

AbstractBy virtue of niche construction traits, plants play a significant role in shaping landscapes. The resultant outcome is a change in the selective environment, which influences the evolution of these same plants. So far almost all biogeomorphic models have assumed that niche construction traits are invariant in time. On the other hand, niche construction studies have assumed that independent abiotic changes are either nonexistent or are simply linear. Here, I considered the concomitant evolution of plant niche construction traits during landscape development. I constructed a geo-evolutionary model that couples a population genetic module with a landscape development module. Allowing plants to evolve always results in landforms different from those that appear when evolution is not accounted for. The topographic difference between cases with and without evolution ranges from a small difference in the steady-state topography, to drastic differences in landforms. The amount of difference is contingent upon forms of landscape development and the strength of geo-evolutionary coupling. Allowing the landscape to develop while evolution occurs changes evolutionary trajectories for niche construction traits. The landscape can even develop spatial structures that suppress selection. Model results clearly support the need to integrate niche construction theory and biogeomorphology to better understand both.
Auxin and pectin remodeling interplay during rootlet emergence in white lupin
Authors: Jobert François , Soriano Alexandre , Brottier Laurent , Casset Célia , Divol Fanchon , Safran Josip , Lefebvre Valérie , Pelloux Jérôme , Robert Stéphanie , Péret Benjamin 
Published: July 2021

AbstractSecondary root emergence is a crucial trait that shapes the plant’s underground system. Virtually every developmental step of root primordium morphogenesis is controlled by auxin. However, how the hormone controls cell separation in primordium-overlaying tissues through wall loosening is poorly understood. Here, we took advantage of white lupin and its spectacular cluster root development to assess the contribution of auxin to this process. We show that auxin’s positive role on rootlet emergence is associated with an upregulation of cell wall pectin modifying and degrading genes. Downregulation of a pectinolytic enzyme gene expressed in cells surrounding the primordium resulted in delayed emergence. Pectins were demethylesterified in the emergence zone and auxin treatment further enhanced this effect. Additionally, we report specific rhamnogalacturonan-I modifications during cortical cell separation. In conclusion, we propose a model in which auxin has a dual role during rootlet emergence: Firstly, through active pectin demethylesterification and secondly by regulating the expression of cell wall remodeling enzymes.
Robust optimization of resource-constrained assembly line balancing problems with uncertain operation times
Authors: Jin Wenrui , He Zhaoxu , Wu Qiong 
Published: July 2021

PurposeDue to the market trend of low-volume and high-variety, the manufacturing industry is paying close attention to improve the ability to hedge against variability. Therefore, in this paper the assembly line with limited resources is balanced in a robust way that has good performance under all possible scenarios. The proposed model allows decision makers to minimize a posteriori regret of the selected choice and hedge against the high cost caused by variability.Design/methodology/approachA generalized resource-constrained assembly line balancing problem (GRCALBP) with an interval data of task times is modeled and the objective is to find an assignment of tasks and resources to the workstations such that the maximum regret among all the possible scenarios is minimized. To properly solve the problem, the regret evaluation, an exact solution method and an enhanced meta-heuristic algorithm, Whale Optimization Algorithm, are proposed and analyzed. A problem-specific coding scheme and search mechanisms are incorporated.FindingsTheory analysis and computational experiments are conducted to evaluated the proposed methods and their superiority. Satisfactory results show that the constraint generation technique-based exact method can efficiently solve instances of moderate size to optimality, and the performance of WOA is enhanced due to the modified searching strategy.Originality/valueFor the first time a minmax regret model is considered in a resource-constrained assembly line balancing problem. The traditional Whale Optimization Algorithm is modified to overcome the inferior capability and applied in discrete and constrained assembly line balancing problems.
Informational content of options around analyst recommendations
Authors: Wang Qingxia , Faff Robert , Zhu Min 
Published: July 2021

PurposeMore studies have investigated the relation between option measures and stock returns during scheduled corporate events. This study adds to the literature and investigates the informational role of options concerning stock returns following unscheduled corporate news events. The authors focus on individual analysts' recommendation changes rather than consensus revisions, as the recommendation consensus might discard a large amount of potentially valuable information in the aggregation process.Design/methodology/approachBased on the econometric model, the authors follow Bakshi et al. (2003) to construct the model-free option implied measures. The authors further decompose the implied option variance into upside and downside components. In such a way, the different informational roles of call and put options can be distinguished. A variety of regression analyses are conducted to examine the predictive power of option implied measures, and the ordered probit model is used to test the tipping hypothesis of analyst recommendations.FindingsThis study’s results show that the option market impounds the “valuable” firm-specific news; thus, the pre-event option market is strongly related to stock returns around recommendations even though recommendation changes are largely “unscheduled”. At the same time, these results suggest that upside (good) and downside (bad) implied volatilities contain distinctive information on subsequent stock returns.Originality/valueThis study provides new evidence that an increase in upside (downside) volatility around analyst recommendation changes would increase the probability that analysts upgrade (downgrade) the stock. The findings provide implications for investors and risk managers in making investment decisions.