bluuebunny/crossref_metadata_2025_split huggingface dataset:
The In Vivo Source of Type I and Type III IFNs is Pathogen Dependent
Authors: Sandoval Marvin J. , Tseng Hsiang-Chi , Risman Heidi P. , Smirnov Sergey , Li Qing , Lin Jian-Da , Rivera Amariliz , Durbin Russell K. , Kotenko Sergei V. , Durbin Joan E. 
Published: October 2021

AbstractType I (-α, β) and type III (-λ) interferons (IFNs) are produced in response to virus infection and upregulate a largely overlapping set of IFN stimulated genes which mediate the protective effects of these antiviral cytokines. In vitro studies have demonstrated the redundancy of these two cytokine families which activate the same transcription factor, IFN stimulated gene factor 3 (ISGF3), via distinct ligands and receptors. However, in vivo, these IFN types do have distinct functions based on receptor distribution, but also ligand availability. Using a newly generated IFN-λ reporter mouse strain we have observed that both type I and type III IFNs are produced in response to respiratory tract infection by Newcastle disease virus (NDV) and influenza A virus (IAV). In the case of NDV these IFNs are synthesized by different cell types. Type I IFNs are produced primarily by alveolar macrophages, type III IFNs are made only by epithelial cells, and production of either is dependent on MAVS. While epithelial cells of the respiratory tract represent the primary target of IAV infection, we found that they did not significantly contribute to IFN-λ production, and IFN-λ protein levels were largely unaffected in the absence of MAVS. Instead we found that pDCs, a cell type known for robust IFN-α production via TLR/MyD88 signaling, were the major producers of IFN-λ during IAV infection, with pDC depletion during influenza infection resulting in significantly reduced levels of both IFN-α and IFN-λ. In addition, we were able to demonstrate that pDCs rely on type I IFN for optimal IFN-λ production. These studies therefore demonstrate that the in vivo producers of Type III IFNs in response to respiratory virus infection are pathogen dependent, a finding which may explain the varying levels of cytokine production induced by different viral pathogens.
Dedicated chaperones coordinate co-translational regulation of ribosomal protein production with ribosome assembly to preserve proteostasis
Authors: Pillet Benjamin , Méndez-Godoy Alfonso , Murat Guillaume , Favre Sébastien , Stumpe Michael , Falquet Laurent , Kressler Dieter 
Published: October 2021

AbstractThe biogenesis of eukaryotic ribosomes involves the ordered assembly of around 80 ribosomal proteins. Supplying equimolar amounts of assembly-competent ribosomal proteins is complicated by their aggregation propensity and the spatial separation of their location of synthesis and pre-ribosome incorporation. Recent evidence has highlighted that dedicated chaperones protect individual, unassembled ribosomal proteins on their path to the pre-ribosomal assembly site. Here, we show that the co-translational recognition of Rpl3 and Rpl4 by their respective dedicated chaperone, Rrb1 or Acl4, prevents the degradation of the encoding RPL3 and RPL4 mRNAs in the yeast Saccharomyces cerevisiae. In both cases, negative regulation of mRNA levels occurs when the availability of the dedicated chaperone is limited and the nascent ribosomal protein is instead accessible to a regulatory machinery consisting of the nascent-polypeptide associated complex and the Caf130-associated Ccr4-Not complex. Notably, deregulated expression of Rpl3 and Rpl4 leads to their massive aggregation and a perturbation of overall proteostasis in cells lacking the E3 ubiquitin ligase Tom1. Taken together, we have uncovered an unprecedented regulatory mechanism that adjusts the de novo synthesis of Rpl3 and Rpl4 to their actual consumption during ribosome assembly and, thereby, protects cells from the potentially detrimental effects of their surplus production.
A Hierarchical Reinforcement Learning Model Explains Individual Differences in Attentional Set Shifting
Authors: Talwar Anahita , Huys Quentin , Cormack Francesca , Roiser Jonathan P 
Published: October 2021

AbstractAttentional set shifting refers to the ease with which the focus of attention is directed and switched. Cognitive tasks such as CANTAB IED reveal great variation in set shifting ability in the general population, with notable impairments in those with psychiatric diagnoses. The attentional and learning processes underlying this cognitive ability, and how they lead to the observed variation remain unknown. To directly test this, we used a modelling approach on two independent large-scale online general-population samples performing CANTAB IED and psychiatric symptom assessment. We found a hierarchical model that learnt both feature values and dimension attention best explained the data, and that compulsive symptoms were associated with slower learning and higher attentional bias to the first relevant stimulus dimension. This data showcase a new methodology to analyse data from the CANTAB IED task, and suggest a possible mechanistic explanation for the variation in set shifting performance, and its relationship to compulsive symptoms.
Chromatin binding of survivin regulates glucose metabolism in the IFN-γ producing CD4+T cells
Authors: Erlandsson Malin C. , Andersson Karin M.E. , Oparina Nina Y. , Chandrasekaran Venkataragavan , Damdimopoulos Anastasios , Garcia-Bonete Maria-Jose , Einbeigi Zakaria , Silfverswärd Sofia T. , Pekna Marcela , Katona Gergely , Bokarewa Maria I. 
Published: October 2021

AbstractInterferon-gamma (IFNγ) producing T cells develop metabolic adaptation required for their effector functions in tumour biology, autoimmunity and antiviral defence.Using sorted CD4+cells we demonstrated that glycolytic switch and high glucose uptake in IFNγ-producing cells was associated with survivin expression. Inhibition of survivin restored glycolysis by upregulating the transcription of phosphofructokinase PFKFB3 and reducing glucose uptake. Integration of the whole-genome sequencing of the chromatin immunoprecipitated with survivin with transcription changes in CD4+cells after survivin inhibition revealed co-localization of survivin, IRF1 and SMAD3 in the regulatory elements paired to the differentially expressed genes. Western blot demonstrated direct binding of survivin to IRF1 and SMAD3. Functionally, inhibition of survivin repressed IFNγ signalling and activated SMAD3-dependent protein remodelling, which resulted in the effector-to-memory transition of CD4+cells. These findings demonstrate the key role of survivin in IFNγ-dependent metabolic adaptation and identify survivin inhibition as an attractive strategy to counteract these effects.
The structure and robustness of tripartite ecological networks
Authors: Domínguez-García Virginia , Kéfi Sonia 
Published: October 2021

ABSTRACTUntil recently, most ecological network analyses have focused on a single interaction type. In nature, however, diverse interactions co-occur, each of them forming a layer of a ‘multilayer’ network. Data including information on multiple interactions has recently started to emerge, giving us the opportunity to have a first glance at possible commonalities in the structure of these networks. We studied the structural features of 44 tripartite ecological networks from the literature, each composed of two layers of interactions (e.g. herbivory, parasitism, pollination), and investigated their fragility to species losses. We found that the way in which the different layers of interactions are connected to each other affect how perturbations spread in ecological communities. Our results highlight the importance of considering multiple interactions simultaneously to better gauge the robustness of ecological communities to species loss and to more reliably identify the species that are important for robustness.
DetecDiv, a generalist deep-learning platform for automated cell division tracking and survival analysis
Authors: Aspert Théo , Hentsch Didier , Charvin Gilles 
Published: October 2021

AbstractAutomating the extraction of meaningful temporal information from sequences of microscopy images represents a major challenge to characterize dynamical biological processes. So far, strong limitations in the ability to quantitatively analyze single-cell trajectories have prevented large-scale investigations to assess the dynamics of entry into replicative senescence in yeast. Here, we have developed DetecDiv, a microfluidic-based image acquisition platform combined with deep learning-based software for high-throughput single-cell division tracking. We show that DetecDiv can automatically reconstruct cellular replicative lifespans with high accuracy and performs similarly with various imaging platforms and geometries of microfluidic traps. In addition, this methodology provides comprehensive temporal cellular metrics using time-series classification and image semantic segmentation. Last, we show that this method can be further applied to automatically quantify the dynamics of cellular adaptation and the real-time cell survival upon exposure to environmental stress. Hence, this methodology provides an all-in-one toolbox for high-throughput phenotyping for cell cycle, stress response, and replicative lifespan assays.
Engineered natural killer cells impede the immunometabolic CD73-adenosine axis in solid tumors
Authors: Chambers Andrea M. , Lupo Kyle B. , Wang Jiao , Cao Jingming , Toregrosa-Allen Sandra , Elzey Bennett D. , Pine Sharon R. , Jalal Shadia , Utturkar Sagar , Lanman Nadia A. , Bernal-Crespo Victor , Matosevic Sandro 
Published: October 2021

SummaryImmunometabolic reprogramming due to CD73-produced adenosine is a recognized immunosuppressive mechanism contributing to immune evasion in solid tumors. Adenosine is not only known to contribute to tumor progression, but it has specific roles in driving dysfunction of immune cells, including natural killer (NK) cells. Here, we engineered NK cells to directly target the CD73-adenosine axis by blocking the enzymatic activity of CD73. In doing so, the engineered NK cells not only impaired adenosinergic metabolism driven by the hypoxic uptake of ATP by cancer cells, but also mediated killing of tumor cells due to the specific recognition of overexpressed CD73. This results in a “single agent” immunotherapy that combines antibody specificity, blockade of purinergic signaling, and killing of targets mediated by NK cells. We also showed that CD73-targeted NK cells are potent in vivo and result in tumor arrest, while promoting NK cell infiltration into CD73+ tumors and enhanced intratumoral activation.
Riboswitch Folds to Holo-Form Like Structure Even in the Absence of Cognate Ligand at High Mg2+ Concentration
Authors: Kumar Sunil , Reddy Govardhan 
Published: October 2021

AbstractRiboswitches are non-coding RNA that regulate gene expression by folding into specific three-dimensional structures (holo-form) upon binding by their cognate ligand in the presence of Mg2+. Riboswitch functioning is also hypothesized to be under kinetic control requiring large cognate ligand concentrations. We ask the question under thermodynamic conditions, can the riboswitches populate holo-form like structures in the absence of their cognate ligands only in the presence of Mg2+. We addressed this question using thiamine pyrophosphate (TPP) riboswitch as a model system and computer simulations using a coarse-grained model for RNA. The folding free energy surface (FES) shows that with the initial increase in Mg2+ concentration ([Mg2+]), TPP AD undergoes a barrierless collapse in its dimensions. On further increase in [Mg2+], intermediates separated by barriers appear on the FES, and one of the intermediates has a TPP ligand-binding competent structure. We show that site-specific binding of the Mg2+ aids in the formation of tertiary contacts. For [Mg2+] greater than physiological concentration, AD folds into its holo-form like structure even in the absence of the TPP ligand. The folding kinetics shows that it populates an intermediate due to the misalignment of the two arms in the TPP AD, which acts as a kinetic trap leading to larger folding timescales. The predictions of the intermediate structures from the simulations are amenable for experimental verification.
Sequencing of Argonaute-bound miRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a
Authors: Fields Christopher J. , Li Lu , Hiers Nicholas M. , Li Tianqi , Sheng Peike , Huda Taha , Shan Jixiu , Gay Lauren , Gu Tongjun , Bian Jiang , Kilberg Michael S. , Renne Rolf , Xie Mingyi 
Published: October 2021

ABSTRACTMicroRNAs (miRNA) are short non-coding RNAs widely implicated in gene regulation. Most metazoan miRNAs utilize the RNase III enzymes Drosha and Dicer for biogenesis. One notable exception is the RNA polymerase II transcription start sites (TSS) miRNAs whose biogenesis does not require Drosha. The functional importance of the TSS-miRNA biogenesis is uncertain. To better understand the function of TSS-miRNAs, we applied a modifiedCrosslinking,Ligation, andSequencing ofHybrids on Argonaute (AGO-qCLASH) to identify the targets for TSS-miRNAs in HCT116 colorectal cancer cells with or withoutDROSHAknockout. We observed that miR-320a hybrids dominate in TSS-miRNA hybrids identified by AGO-qCLASH. Targets for miR-320a are enriched in the eIF2 signaling pathway, a downstream component of the unfolded protein response. Consistently, in miR-320a mimic- and antagomir- transfected cells, differentially expressed genes are enriched in eIF2 signaling. Within the AGO-qCLASH data, we identified the endoplasmic reticulum (ER) chaperone Calnexin as a direct miR-320a target, thus connecting miR-320a to the unfolded protein response. During ER stress, but not amino acid deprivation, miR-320a up-regulates ATF4, a critical transcription factor for resolving ER stress. Our study investigates the targetome of the TSS-miRNAs in colorectal cancer cells and establishes miR-320a as a regulator of unfolded protein response.
Peripherally targeted analgesia via AAV-mediated sensory neuron-specific inhibition of multiple pronociceptive sodium channels in rat
Authors: Shin Seung Min , Itson-Zoske Brandon , Qiu Chensheng , Rahman Mahmudur , Gani Uarda , Fan Fan , Cummins Theodore R. , Hogan Quinn H. , Yu Hongwei 
Published: October 2021

AbstractThis study reports that targeting intrinsically disordered regions (IDRs) of NaV1.7 protein facilitated discovery of sodium channel inhibitory peptide aptamers (NaviPA) for adeno-associated virus (AAV)-mediated, sensory neuron-specific analgesia. A multipronged inhibition of INa1.7, INa1.6, and INa1.3, but not INa1.5and INa1.8was found for a prototype, named NaviPA1, which was derived from the NaV1.7 intracellular loop 1 and is conserved among the TTXs NaVsubtypes. NaviPA1 expression in primary sensory neurons (PSNs) of dorsal root ganglia (DRG) produced significant inhibition of TTXs INabut not TTXr INa. DRG injection of AAV6-encoded NaviPA1 significantly attenuated evoked and spontaneous pain behaviors in both male and female rats with neuropathic pain induced by tibial nerve injury (TNI). Whole-cell current-clamp of the PSNs showed that NaviPA1 expression normalized PSN excitability in TNI rats, suggesting that NaviPA1 attenuated pain by reversal of injury-induced neuronal hypersensitivity. Immunohistochemistry revealed efficient NaviPA1 expression restricted in PSNs and their central and peripheral terminals, indicating PSN-restricted AAV biodistribution. Inhibition of sodium channels by NaviPA1 was replicated in the human iPSC-derived sensory neurons. These results summate that NaviPA1 is a promising analgesic lead that, combined with AAV-mediated PSN-specific block of multiple TTXs NaVs has potential as peripheral nerve-restricted analgesic therapeutics.
Quantitative modeling of fine-scale variations in theArabidopsis thalianacrossover landscape
Authors: Hsu Yu-Ming , Falque Matthieu , Martin Olivier C. 
Published: October 2021

AbstractIn essentially all species where meiotic crossovers have been studied, they occur preferentially in open chromatin, typically near gene promoters and to a lesser extent at the end of genes. Here, in the case ofArabidopsis thaliana, we unveil further trends arising when one considers contextual information, namely summarized epigenetic status, size of underlying genomic regions and degree of divergence between homologs. For instance we find that intergenic recombination rate is reduced if those regions are less than 1.5 kb in size. Furthermore, we propose that the presence of single nucleotide polymorphisms is a factor driving enhanced crossover rate compared to when homologous sequences are identical, in agreement with previous works comparing rates in homozygous and heterozygous blocks. Lastly, by integrating these different factors, we produce a quantitative and predictive model of the recombination landscape that reproduces much of the experimental variation.
Machine Learning Speeding Up the Development of Portfolio of New Crop Varieties to Adapt to and Mitigate Climate Change
Authors: Bari A. , Ouabbou H. , Jilal A. , Khazaei H. , Stoddard F.L. , Sillanpää M.J. 
Published: October 2021

AbstractClimate change poses serious challenges to achieving food security in a time of a need to produce more food to keep up with the world’s increasing demand for food. There is an urgent need to speed up the development of new high yielding varieties with traits of adaptation and mitigation to climate change. Mathematical approaches, including ML approaches, have been used to search for such traits, leading to unprecedented results as some of the traits, including heat traits that have been long sought-for, have been found within a short period of time.
Model to measure the effect of the integration of information in business processes. Example: bidding process for an industry
Authors: Rodríguez-Rios Claudia Yadira , Roa-Sánchez Jorge Enrique 
Published: October 2021

PurposeThe main contribution of the research is to propose a quantitative model based on indicators designed by the authors, to measure the effect on the performance of the process caused by an improvement in the integration of information.Design/methodology/approachIt is a descriptive and exploratory investigation, immersed in a case study; the bidding process was selected by senior management due to the high complexity and impact of this process on the organization. The protocol for carrying out the study involved interviews with the owner of the process and all the officials involved, as sources of information, inputs to model in BPMN2.0 at the activity level and a statistical validation of the model was carried out, to sustain an acceptable confidence of the same.FindingsAmong the most outstanding results of the research are that the effects of the improvements or changes in the activities were reflected or evidenced in subsequent activities, not in the immediate ones or in which the improvement is applied. This confirms the theorization of the systemic approach to processes since the effects of the improvements are not close to their application.Research limitations/implicationsFor the proposed model, it was evident that the measurement of the efficiency and quality dimensions of the process activities required verification in transactional databases where nonconformities and nonquality costs related to orders are recorded.Originality/valueIn the reviewed literature, there are no models or reference frameworks that quantitatively measure the effects of the integration of information on the performance of processes.
Experimental studies on the development of a self-healing cementitious matrix for repair and retrofitting of concrete structures
Authors: Adak Dibyendu , Marbaniang Donkupar Francis , Dutta Subhrajit 
Published: October 2021

PurposeSelf-healing concrete is a revolutionary building material that will generally reduce the maintenance cost of concrete constructions. Self-healing of cracks in concrete structure would contribute to a longer service life of the concrete and would make the material more durable and more sustainable. The cementitious mortar with/without incorporating encapsulates at different percentages of slag replacement with the cement mix improves autogenous healing at different ages. Therefore, this study’s aim is to develop a self-healing cementitious matrix for repair and retrofitting of concrete structures.Design/methodology/approachIn the present work, waste straw pipes are used as a capsule, filled with the solution of sodium hydroxide (NaOH), sodium silicate (Na2SiO3) and colloidal nano-silica as self-healing activators. An artificial micro-crack on the control and blended mortar specimens at different percentages of slag replacement with cement (with/without encapsulation) is developed by applying a compressive load of 50% of its ultimate load-carrying capacity. The mechanical strength and ultrasonic pulse velocity, water absorption and chloride ion penetration test are conducted on the concrete specimen before and after the healing period. Finally, the self-healing activity of mortar mixes with/without encapsulation is analysed at different ages.FindingsThe encapsulated mortar mix with 10% of slag content has better self-healing potential than all other mixes considering mechanical strength and durability. The enhancement of the self-healing potential of such mortar mix is mainly due to hydration of anhydrous slag on the crack surface and transformation of amorphous slag to the crystalline phase in presence of encapsulated fluid.Research limitations/implicationsThe self-healing activities of the slag-based cementitious composite are studied for a healing period of 90 days only. The strength and durability performance of the cracked specimen may be increased after a long healing period.Practical implicationsThe outcome of the work will help repair the cracks in the concrete structure and enhances the service life.Originality/valueThis study identifies the addition encapsulates with a self-healing activator fluid that can recover its strength after minor damage.
The effect of knowledge management on intellectual capital, social capital, and firm innovation
Authors: Salehi Mahdi , Fahimi Mohammad Ali , Zimon Grzegorz , Homayoun Saeid 
Published: October 2021

PurposeThis study aims to analyze the literature on knowledge management on intellectual capital, social capital and its contribution to Iranian companies’ innovation.Design/methodology/approachTo investigate knowledge management’s relationship on intellectual capital, social capital and innovation, using structural equation modeling based on data collected from 205 chief executive officers, production managers and marketing managers of Iranian companies. The research instrument is a standard questionnaire consisting of 109 questions in which 5 of them are demographic questions, 26 questions were asked to reveal the knowledge management process, 40 questions for intellectual capital, 21 for social capital and 17 for innovation.FindingsThe results show that knowledge management has a positive and significant relationship between intellectual capital and social capital. Knowledge management did not have a significant effect on innovation. However, intellectual capital and social capital have a significant effect on innovation. On the other hand, knowledge management mediated by intellectual capital and social capital has a positive and significant indirect effect on innovation.Originality/valueThe paper includes the implications for developing knowledge management and intellectual, social capital leading to innovation in manufacturing companies. Knowledge management can improve the innovation performance of a company if it is shared and applied effectively. This study addresses an important subject and the findings may be used by professionals and managers or another person interested in advancing knowledge management that leads to innovation.