bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Broadly Conserved Deoxycytidine Deaminase Protects Bacteria from Phage Infection
Authors: Severin Geoffrey B. , Hsueh Brian Y. , Elg Clinton A. , Dover John A. , Rhoades Christopher R. , Wessel Alex J. , Ridenhour Benjamin J. , Top Eva M. , Ravi Janani , Parent Kristin N. , Waters Christopher M. 
Published: April 2021

SUMMARYThe El Tor biotype ofVibrio choleraeis responsible for perpetuating the longest cholera pandemic in recorded history (1961-current). The genomic islands VSP-1 and -2 are two understudied genetic features that distinguish El Tor from previous pandemics. To understand their utility, we calculated the co-occurrence of VSP genes across bacterial genomes. This analysis predicted the previously uncharacterizedvc0175, herein renameddeoxycytidylatedeaminaseVibrio(dcdV), is in a gene network withdncV, a cyclic GMP-AMP synthase involved in phage defense. DcdV consists of two domains, a P-loop kinase and a deoxycytidylate deaminase, that are required for the deamination of dCTP and dCMP, inhibiting phage predation by corrupting cellular nucleotide concentrations. Additionally, DcdV is post-translationally inhibited by a unique noncoding RNA encoded 5’ of thedcdVlocus. DcdV homologs are conserved in bacteria and eukaryotes and our results identifyV. choleraeDcdV as the founding member of a previously undescribed bacterial phage defense system.
Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity
Authors: Correia Jorge C. , Kelahmetoglu Yildiz , Jannig Paulo R. , Schweingruber Christoph , Svaikovskaya Dasa , Zhengye Liu , Cervenka Igor , Oliveira Mariana , Nijssen Jik , Martínez-Redondo Vicente , Stec Michael , Khan Naveen , Lanner Johanna T. , Kleiner Sandra , Hedlund Eva , Ruas Jorge L. 
Published: April 2021

SUMMARYEndurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA-sequencing of MN somas, we observed that retrograde NRTN signaling promotes a shift towards a slow MN identity. In muscle, NRTN increased capillary density, oxidative capacity, and induced a transcriptional reprograming favoring fatty acid metabolism over glycolysis. This combination of effects on muscle and MNs, makes HSA-NRTN mice lean with remarkable exercise performance and motor coordination. Interestingly, HSA-NRTN mice largely recapitulate the phenotype of mice with muscle-specific expression of its upstream regulator PGC-1α1. This work identifies NRTN as a myokine that couples muscle oxidative capacity to slow MN identity.HIGHLIGHTSNRTN is a myokine induced by physical exercise.Muscle-derived NRTN promotes a slow motor neuron identity.Muscle-derived NRTN enhances muscle oxidative metabolism.NRTN improves systemic metabolism, exercise performance and motor coordination.
Neural correlates of blood flow measured by ultrasound
Authors: Nunez-Elizalde Anwar O. , Krumin Michael , Bai Reddy Charu , Montaldo Gabriel , Urban Alan , Harris Kenneth D. , Carandini Matteo 
Published: April 2021

SummaryFunctional ultrasound imaging (fUSI) is a popular method for measuring blood flow and thus infer brain activity, but it relies on the physiology of neurovascular coupling and requires extensive signal processing. To establish to what degree its trial-by-trial signals reflect neural activity, we performed simultaneous fUSI and neural recordings with Neuropixels probes in awake mice. fUSI signals strongly correlated with the slow (<0.3 Hz) fluctuations in local firing rate, and were closely predicted by the smoothed firing rate of local neurons, particularly putative inhibitory neurons. The optimal smoothing filter had width ~3 s, matched the hemodynamic response function of awake mouse, was invariant across mice and stimulus conditions, and similar in cortex and hippocampus. fUSI signals also matched neural firing spatially: firing rates were as highly correlated across hemispheres as fUSI signals. Thus, hemodynamic signals measured by ultrasound bear a simple and accurate relationship to neuronal firing.
Structural dynamics of the β-coronavirus Mpro protease ligand binding sites
Authors: Cho Eunice , Rosa Margarida , Anjum Ruhi , Mehmood Saman , Soban Mariya , Mujtaba Moniza , Bux Khair , Dantu Sarath , Pandini Alessandro , Yin Junqi , Ma Heng , Ramanathan Arvind , Islam Barira , Mey Antonia S J S , Bhowmik Debsindhu , Haider Shozeb 
Published: April 2021

Abstractβ-coronaviruses alone have been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a back-up against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensible role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide a comprehensive comparison of all non-redundant ligand-binding sites available for SARS-CoV2, SARS-CoV and MERS-CoV Mpro. Extensive adaptive sampling has been used to explore conformational dynamics employing convolutional variational auto encoder-based deep learning, and investigates structural conservation of the ligand binding sites using Markov state models across β-coronavirus homologs. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-coronavirus homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor.
Age differences in the functional architecture of the human brain
Authors: Setton Roni , Mwilambwe-Tshilobo Laetitia , Girn Manesh , Lockrow Amber W. , Baracchini Giulia , Hughes Colleen , Lowe Alexander J. , Cassidy Benjamin N. , Li Jian , Luh Wen-Ming , Bzdok Danilo , Leahy Richard M. , Ge Tian , Margulies Daniel S. , Misic Bratislav , Bernhardt Boris C. , Stevens W. Dale , De Brigard Felipe , Kundu Prantik , Turner Gary R. , Spreng R. Nathan 
Published: April 2021

AbstractThe intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience dependent changes, or both, is uncertain. We employed a multi-method strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n=181) and older (n=120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant, while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multi-scale, multi-method approaches to characterize the architecture of functional brain aging.
Influence of substrate stiffness on barrier function in an iPSC-derived in vitro blood-brain barrier model
Authors: Bosworth Allison M. , Kim Hyosung , O’Grady Kristin P. , Richter Isabella , Lee Lynn , O’Grady Brian J. , Lippmann Ethan S. 
Published: April 2021

ABSTRACTIntroductionVascular endothelial cells respond to a variety of biophysical cues such as shear stress and substrate stiffness. In peripheral vasculature, extracellular matrix (ECM) stiffening alters barrier function, leading to increased vascular permeability in atherosclerosis and pulmonary edema. The effect of ECM stiffness on blood-brain barrier (BBB) endothelial cells, however, has not been explored. To investigate this topic, we incorporated hydrogel substrates into an in vitro model of the human BBB.MethodsInduced pluripotent stem cells were differentiated to brain microvascular endothelial-like (BMEC-like) cells and cultured on hydrogel substrates of varying stiffness. Cellular changes were measured by imaging, functional assays such as transendothelial electrical resistance (TEER) and p-glycoprotein efflux activity, and bulk transcriptome readouts.ResultsThe magnitude and longevity of TEER in iPSC-derived BMEC-like cells is enhanced on compliant substrates. Quantitative imaging shows that BMEC-like cells form fewer intracellular actin stress fibers on substrates of intermediate stiffness (20 kPa relative to 1 kPa and 150 kPa). Chemical induction of actin polymerization leads to a rapid decline in TEER, agreeing with imaging readouts. P-glycoprotein activity is unaffected by substrate stiffness. Modest differences in RNA expression corresponding to specific signaling pathways were observed as a function of substrate stiffness.ConclusionsiPSC-derived BMEC-like cells exhibit differences in passive but not active barrier function in response to substrate stiffness. These findings may provide insight into BBB dysfunction during neurodegeneration, as well as aid in the optimization of more complex threedimensional neurovascular models utilizing compliant hydrogels.
OME-NGFF: scalable format strategies for interoperable bioimaging data
Authors: Moore Josh , Allan Chris , Besson Sebastien , Burel Jean-Marie , Diel Erin , Gault David , Kozlowski Kevin , Lindner Dominik , Linkert Melissa , Manz Trevor , Moore Will , Pape Constantin , Tischer Christian , Swedlow Jason R. 
Published: April 2021

SummaryBiological imaging is one of the most innovative fields in the modern biological sciences. New imaging modalities, probes, and analysis tools appear every few months and often prove decisive for enabling new directions in scientific discovery. One feature of this dynamic field is the need to capture new types of data and data structures. While there is a strong drive to make scientific data Findable, Accessible, Interoperable and Reproducible (FAIR1), the rapid rate of innovation in imaging impedes the unification and adoption of standardized data formats. Despite this, the opportunities for sharing and integrating bioimaging data and, in particular, linking these data to other “omics” datasets have never been greater. Therefore, to every extent possible, increasing “FAIRness” of bioimaging data is critical for maximizing scientific value, as well as for promoting openness and integrity.In the absence of a common, FAIR format, two approaches have emerged to provide access to bioimaging data: translation and conversion. On-the-fly translation produces a transient representation of bioimage metadata and binary data but must be repeated on each use. In contrast, conversion produces a permanent copy of the data, ideally in an open format that makes the data more accessible and improves performance and parallelization in reads and writes. Both approaches have been implemented successfully in the bioimaging community but both have limitations. At cloud-scale, those shortcomings limit scientific analysis and the sharing of results. We introduce here next-generation file formats (NGFF) as a solution to these challenges.
Attention improves information flow between neuronal populations without changing the communication subspace
Authors: Srinath Ramanujan , Ruff Douglas A. , Cohen Marlene R. 
Published: April 2021

SummaryVisual attention allows observers to flexibly use or ignore visual information, suggesting that information can be flexibly routed between visual cortex and neurons involved in decision-making. We investigated the neural substrate of flexible information routing by analyzing the activity of populations of visual neurons in the medial temporal area (MT) and oculomotor neurons in the superior colliculus (SC) while rhesus monkeys switched spatial attention. We demonstrated that attention increases the efficacy of visuomotor communication: trial-to-trial variability of the population of SC neurons was better predicted by the activity of MT neurons (and vice versa) when attention was directed toward their joint receptive fields. Surprisingly, this improvement in prediction was not explained or accompanied by changes in the dimensionality of the shared subspace or in local or shared pairwise noise correlations. These results suggest a mechanism by which visual attention can affect perceptual decision-making without altering local neuronal representations.
The Time Complexity of Self-Assembly
Authors: Gartner Florian M. , Graf Isabella R. , Frey Erwin 
Published: April 2021

ABSTRACTTime efficiency of self-assembly is crucial for many biological processes. Moreover, with the advances of nanotechnology, time efficiency in artificial self-assembly becomes ever more important. While structural determinants and the final assembly yield are increasingly well understood, kinetic aspects concerning the time efficiency, however, remain much more elusive. In computer science, the concept oftime complexityis used to characterize the efficiency of an algorithm and describes how the algorithm’s runtime depends on the size of the input data. Here we characterize the time complexity of non-equilibrium self-assembly processes by exploring how the time required to realize a certain, substantial yield of a given target structure scales with its size. We identify distinct classes of assembly scenarios, i.e. ‘algorithms’ to accomplish this task, and show that they exhibit drastically different degrees of complexity. Our analysis enables us to identify optimal control strategies for non-equilibrium self-assembly processes. Furthermore, we suggest an efficient irreversible scheme for the artificial self-assembly of nanostructures, which complements the state-of-the-art approach using reversible binding reactions and requires no fine-tuning of binding energies.
Tissue specific requirements for ECSIT in mitochondrial complex I assembly
Authors: Nicol Thomas L , Falcone Sara , Blease Andrew , Vikhe Pratik , Civiletto Gabriele , Omairi Saleh Salman , Viscomi Carlo , Patel Ketan , Potter Paul K 
Published: April 2021

AbstractHere we describe a mutation in the mitochondrial complex I assembly factor (Evolutionarily conserved signalling intermediate in Toll pathway) ECSIT which reveals tissue specific requirements for this factor in complex I assembly. Mitochondrial complex I assembly is a multi-step process dependant on assembly factors that organise and arrange the individual subunits, allowing for their incorporation into the complete enzyme complex. We have identified an ENU induced mutation in ECSIT (N209I) that exhibits a profound effect on complex I assembly only in heart tissue resulting in hypertrophic cardiomyopathy in the absence of other phenotypes. Mitochondrial function was reduced by 98% in mitochondria isolated from cardiac tissue but mitochondria from other tissues such as skeletal muscle, brain, liver, and kidney were unaffected. This data suggests the mechanisms underlying complex I assembly are tissue specific and has implications in understanding the pathogenesis of cardiomyopathy.
Acylation of the incretin peptide exendin-4 directly impacts GLP-1 receptor signalling and trafficking
Authors: Lucey Maria , Ashik Tanyel , Marzook Amaara , Wang Yifan , Goulding Joëlle , Oishi Atsuro , Broichhagen Johannes , Hodson David J , Minnion James , Elani Yuval , Jockers Ralf , Briddon Stephen J , Bloom Stephen R , Tomas Alejandra , Jones Ben 
Published: April 2021

AbstractThe glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor and mainstay therapeutic target for the treatment of type 2 diabetes and obesity. Recent reports have highlighted how biased agonism at the GLP-1R affects sustained glucose-stimulated insulin secretion through avoidance of desensitisation and downregulation. A number of GLP-1R agonists (GLP-1RAs) feature a fatty acid moiety to promote albumin binding in order to prolong their pharmacokinetics, but the potential for these ligand changes to influence GLP-1R signalling has rarely been investigated beyond potency assessments for cyclic adenosine monophosphate (cAMP). In this work we directly compare the prototypical GLP-1RA exendin-4 with its C-terminally acylated analogue, exendin-4-C16, for their relative propensities to recruit and activate G proteins and β-arrestins, endocytic and post-endocytic trafficking profiles, and interactions with model and cellular membranes. Both ligands had similar cAMP potency but the exendin-4-C16 showed ∼2.5-fold bias towards G protein recruitment and a ∼60% reduction in β-arrestin-2 recruitment efficacy compared to exendin-4, as well as reduced GLP-1R endocytosis and preferential targeting towards recycling pathways. These effects were associated with a reduced ability to promote the movement of the GLP-1R extracellular domain, as determined using a conformational biosensor approach, and a ∼70% increase in insulin secretion. Interactions with plasma membrane lipids were enhanced by the acyl chain. Exendin-4-C16 showed extensive albumin binding and was highly effective for lowering of blood glucose in mice over at least 72 hours. Overall, our study highlights the importance of a broad approach to the evaluation of GLP-1RA pharmacology.Significance statementAcylation is a common strategy to enhance the pharmacokinetics of peptide-based drugs. Our work shows how acylation can also affect various other pharmacological parameters, including biased agonism, receptor trafficking and interactions with the plasma membrane, which may be therapeutically important.
Sustainability rating and moral fictionalism: opening the black box of nonfinancial agencies
Authors: Boiral Olivier , Talbot David , Brotherton Marie-Christine , Heras-Saizarbitoria Iñaki 
Published: April 2021

PurposeThe purpose of this paper is to explore the practices, challenges and ethical issues underlying the fabric and dissemination of corporate sustainability ratings.Design/methodology/approachBased on 36 semi-structured interviews with sustainability rating practitioners, the study shows the trade-offs, ethical judgments and customizable aspects involved in rating practices, which cannot rely only on formal and predefined methods.FindingsIn contrast with the official optimistic rhetoric about the rationality and rigor of sustainability rating methods, agencies face serious challenges in the measurement and comparison of performance in this area, particularly in terms of the aggregation of scattered and fuzzy indicators, commercial pressures and the availability, materiality and reliability of the information collected. Despite these concerns, sustainability ratings do appear to be useful in improving corporate responsiveness and increasing investor awareness of the complex and difficult-to-measure aspects of nonfinancial reports.Practical implicationsRating agencies should collaborate to set up common indicators that would be easier for firms to produce and should better separate their sustainability rating production activities from other services they offer to companies (e.g. consultancy).Originality/valueThis study contributes to the literature on the measurement and promotion of corporate sustainability by analyzing rating practices through the lens of moral fictionalism, which here refers to the human tendency to build ethical judgments on fictional but convenient and useful representations.
Artificial intelligence video interviewing for employment: perspectives from applicants, companies, developer and academicians
Authors: Kim Jin-Young , Heo WanGyu 
Published: April 2021

PurposeIn 2018, an artificial intelligence (AI) interview platform was introduced and adopted by companies in Korea. This study aims to explore the perspectives of applicants who have experienced an AI-based interview through this platform and examines the opinions of companies, a platform developer and academia.Design/methodology/approachThis study uses a phenomenological approach. The participants, who had recent experience of AI video interviews, were recruited offline and online. Eighteen job applicants in their 20s, two companies that have adopted this interview platform, a software developer who created the platform and three professors participated in the study. To collect data, focus group interviews and in-depth interviews were conducted.FindingsAs a result, all of them believed that an AI-based interview was more efficient than a traditional one in terms of cost and time savings and is likely to be adopted by more companies in the future. They pointed to the possibility of data bias requiring an improvement in AI accountability. Applicants perceived an AI-based interview to be better than traditional evaluation procedures in procedural fairness, objectivity and consistency of algorithms. However, some applicants were dissatisfied about being assessed by AI. Digital divide and automated inequality were recurring themes in this study.Originality/valueThe study is important, as it addresses the real application of AI in detail, and a case study of smart hiring tools would be valuable in finding the practical and theoretical implications of such hiring in the fields of employment and AI.
E-participation decision across different channels
Authors: Yao Yurong , Xu Peng 
Published: April 2021

PurposeThis study focuses on understanding how channel features can affect people's intention to continue to use an electronic channel in public affairs and their recommendation behaviors. Specifically, three different channels are focused on: email, microblogs and online meetings.Design/methodology/approachA research model on an e-participation channel based on the channel-disposition framework was developed and an online survey was conducted to collect data from 397 individuals who used three e-participation channels to validate seven hypotheses.FindingsThe study found that information quality, channel interaction quality and the social appearance of other citizens all had a significant impact on users' intention to continue to use an electronic channel, which, in turn, affected their recommendation behaviors. However, the impact differed across the three e-participation channels. Information quality had a stronger impact on microblog and online meeting users' intention to continue to use these channels than on email users' intention to continue using email to participate in public affairs. Channel interaction quality had a stronger impact on email users' intention to continue to use email than on microblog and online meeting users' intention to continue to use these channels in public affairs.Originality/valueThis study helps better explain how various channels and their features can affect participants' use intentions and behaviors in e-participation. It also provides practical guidance for government to better manage e-participation channels and effectively engage citizens in public affairs.