bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-specific T-cell responses reflect substantive in vivo interactions with infected cells despite long-term therapy
Authors: Stevenson Eva M. , Ward Adam R. , Truong Ronald , Thomas Allison S. , Huang Szu-Han , Dilling Thomas R. , Terry Sandra , Bui John K. , Mota Talia M. , Danesh Ali , Lee Guinevere Q. , Gramatica Andrea , Khadka Pragya , Alberto Winiffer D. Conce , Gandhi Rajesh T. , McMahon Deborah K. , Lalama Christina M. , Bosch Ronald J. , Macatangay Bernard , Cyktor Joshua C. , Eron Joseph J. , Mellors John W. , Jones R. Brad ,   for the ACTG A5321 Team
Published: August 2020

AbstractAntiretroviral therapies (ART) durably suppress HIV replication to undetectable levels – however, infection persists in the form of long-lived reservoirs of infected cells with integrated proviruses, that re-seed systemic replication if ART is interrupted. A central tenet of our current understanding of this persistence is that infected cells are shielded from immune recognition and elimination through a lack of antigen expression from proviruses. Efforts to cure HIV infection have therefore focused on reactivating latent proviruses to enable immune-mediated clearance, but these have yet to succeed in driving reductions in viral reservoirs. Here, we revisited the question of whether HIV reservoirs are predominately immunologically silent from a new angle, by querying the dynamics of HIV-specific T-cell responses over long-term ART for evidence of ongoing recognition of HIV-infected cells. We show that T-cell responses to autologous reservoir viruses persist over years, and that the maintenance of HIV-Nef-specific responses was uniquely associated with residual frequencies of infected cells. These responses disproportionately exhibited a cytotoxic, effector functional profile, indicative of recentin vivorecognition of HIV-infected cells. These results indicate substantial visibility of the HIV reservoir to T-cells on stable ART, presenting both opportunities and challenges for the development of therapeutic approaches to curing HIV infection.
Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size
Authors: Swaffer Matthew P. , Chandler-Brown Devon , Kim Jacob , Langhinrichs Maurice , Marinov Georgi , Greenleaf William , Kundaje Anshul , Schmoller Kurt M. , Skotheim Jan M. 
Published: August 2020

SummaryBiosynthesis scales with cell size such that protein concentrations generally remain constant as cells grow. As an exception, synthesis of the cell-cycle inhibitor Whi5 ‘sub-scales’ with cell size so that its concentration is lower in larger cells to promote cell-cycle entry. Here, we find that a transcriptional control uncouples Whi5 synthesis from cell size and, screening for similar genes, identify histones as the major class of sub-scaling transcripts besidesWHI5. Histone synthesis is thereby matched to genome content rather than cell size. Such sub-scaling proteins are challenged by asymmetric cell division because proteins are typically partitioned in proportion to new-born cell volume. To avoid this fate, Whi5 uses chromatin-binding to partition similar protein amounts to each new-born cell regardless of cell size. Finally, disrupting both Whi5 synthesis and chromatin-based partitioning compromises G1 size control. Thus, specific transcriptional and partitioning mechanisms determine protein sub-scaling to control cell size.
A comparative analysis of SARS-CoV-2 antivirals in human airway models characterizes 3CLproinhibitor PF-00835231 as a potential new treatment for COVID-19
Authors: de Vries Maren , Mohamed Adil S , Prescott Rachel A , Valero-Jimenez Ana M , Desvignes Ludovic , O’Connor Rebecca , Steppan Claire , Devlin Joseph C , Ivanova Ellie , Herrera Alberto , Schinlever Austin , Loose Paige , Ruggles Kelly , Koralov Sergei B , Anderson Annaliesa S. , Binder Joseph , Dittmann Meike 
Published: August 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CLpro(Mpro). The drug candidate PF-00835231 is the active compound of the first anti-3CLproregimen in clinical trials. Here, we perform a comparative analysis of PF-00835231, the pre-clinical 3CLproinhibitor GC-376, and the polymerase inhibitor remdesivir, in alveolar basal epithelial cells modified to express ACE2 (A549+ACE2cells). We find PF-00835231 with at least similar or higher potency than remdesivir or GC-376. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps in A549+ACE2cells and validates PF-00835231’s early time of action. In a model of the human polarized airway epithelium, both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 at low micromolar concentrations. Finally, we show that the efflux transporter P-glycoprotein, which was previously suggested to diminish PF-00835231’s efficacy based on experiments in monkey kidney Vero E6 cells, does not negatively impact PF-00835231 efficacy in either A549+ACE2cells or human polarized airway epithelial cultures. Thus, our study providesin vitroevidence for the potential of PF-00835231 as an effective SARS-CoV-2 antiviral and addresses concerns that emerged based on prior studies in non-humanin vitromodels.ImportanceThe arsenal of SARS-CoV-2 specific antiviral drugs is extremely limited. Only one direct-acting antiviral drug is currently approved, the viral polymerase inhibitor remdesivir, and it has limited efficacy. Thus, there is a substantial need to develop additional antiviral compounds with minimal side effects and alternate viral targets. One such alternate target is its main protease, 3CLpro(Mpro), an essential component of the SARS-CoV-2 life cycle processing the viral polyprotein into the components of the viral polymerase complex. In this study, we characterize a novel antiviral drug, PF-00835231, which is the active component of the first-in-class 3CLpro-targeting regimen in clinical trials. Using 3Din vitromodels of the human airway epithelium, we demonstrate the antiviral potential of PF-00835231 for inhibition of SARS-CoV-2.
A Novel Factor in Olfactory Ensheathing Cell-Astrocyte Crosstalk: Anti-Inflammatory Protein α-Crystallin B
Authors: Saglam Aybike , Calof Anne L. , Wray Susan 
Published: August 2020

AbstractAstrocytes are key players in CNS neuroinflammation and neuroregeneration that may help or hinder recovery, depending on the context of the injury. Although pro-inflammatory factors that promote astrocyte-mediated neurotoxicity have been shown to be secreted by reactive microglia, anti-inflammatory factors that suppress astrocyte activation are not well-characterized. Olfactory ensheathing cells (OECs), glial cells that wrap axons of olfactory sensory neurons, have been shown to moderate astrocyte reactivity, creating an environment conducive to regeneration. Similarly, astrocytes cultured in medium conditioned by cultured OECs (OEC-CM) show reduced nuclear translocation of Nuclear Factor kappa-B (NFκB), a pro-inflammatory protein that induces neurotoxic reactivity in astrocytes. In this study, we screened primary and immortalized OEC lines to identify these factors and discovered that Alpha B-crystallin (CryAB), an antiinflammatory protein, is secreted by OECs via exosomes, coordinating an intercellular immune response. Our results showed: 1) OEC exosomes block nuclear NFκB translocation in astrocytes while exosomes fromCryAB-null OECs could not; 2) OEC exosomes could be taken up by astrocytes and 3) CryAB treatment suppressed multiple neurotoxicity-associated astrocyte transcripts. Our results indicate that OEC-secreted factors are potential agents that can ameliorate, or even reverse, the growth-inhibitory environment created by neurotoxic reactive astrocytes following CNS injuries.Main PointsAstrocytes uptake OEC-secreted exosomes.WT OEC-exosomes, but not CryAB-null OEC-exosomes, block nuclear NFκB translocation in astrocytes.CryAB, and other factors secreted by OECs, suppresses multiple neurotoxicity-associated astrocyte transcripts.
Correct regionalisation of a tissue primordium is essential for coordinated morphogenesis
Authors: Sanchez-Corrales Yara E. , Blanchard Guy , Röper Katja 
Published: August 2020

AbstractDuring organ development, tubular organs often form from flat epithelial primordia. In the placodes of the forming tubes of the salivary glands in theDrosophilaembryo, we previously identified spatially defined cell behaviours of cell wedging, tilting and cell intercalation that are key to the initial stages of tube formation. Here we address what the requirements are that ensure the continuous formation of a narrow symmetrical tube from an initially asymmetrical primordium whilst overall tissue geometry is constantly changing. We are using live-imaging and quantitative methods to compare wild-type and mutants that either show disrupted cell behaviours or an initial symmetrical placode organisation, with both resulting in severe impairment of the invagination. We find that early transcriptional patterning of key morphogenetic transcription factors drives the selective activation of downstream morphogenetic modules, such as GPCR signalling that activates apical-medial actomyosin activity to drive cell wedging at the future asymmetrically-placed invagination point. Over time, transcription of key factors expands across the rest of the placode and cells switch their behaviour from predominantly intercalating to predominantly apically constricting as their position approaches the invagination pit. Misplacement or enlargement of the initial invagination pit leads to early problems in cell behaviours that eventually result in a defective organ shape. Our work illustrates that the dynamic patterning of the expression of transcription factors and downstream morphogenetic effectors ensures positionally fixed areas of cell behaviour with regards to the invagination point. This patterning in combination with the asymmetric geometrical set-up ensures functional organ formation.
The spectrum of covariance matrices of randomly connected recurrent neuronal networks
Authors: Hu Yu , Sompolinsky Haim 
Published: September 2020

AbstractA key question in theoretical neuroscience is the relation between the connectivity structure and the collective dynamics of a network of neurons. Here we study the connectivity-dynamics relation as reflected in the distribution of eigenvalues of the covariance matrix of the dynamic fluctuations of the neuronal activities, which is closely related to the network’s Principal Component Analysis (PCA) and the associated effective dimensionality. We consider the spontaneous fluctuations around a steady state in a randomly connected recurrent network of stochastic neurons. An exact analytical expression for the covariance eigenvalue distribution in the large-network limit can be obtained using results from random matrices. The distribution has a finitely supported smooth bulk spectrum and exhibits an approximate power-law tail for coupling matrices near the critical edge. We generalize the results to include connectivity motifs and discuss extensions to Excitatory-Inhibitory networks. The theoretical results are compared with those from finite-size networks and and the effects of temporal and spatial sampling are studied. Preliminary application to whole-brain imaging data is presented. Using simple connectivity models, our work provides theoretical predictions for the covariance spectrum, a fundamental property of recurrent neuronal dynamics, that can be compared with experimental data.
Intensive granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis
Authors: Mizutani Yoko , Fujii Kento , Kawamura Miho , Inoue Madoka , Mizutani Yuki H. , Matsuyama Kanako , Doi Tomoaki , Nagaya Soichiro , Seishima Mariko 
Published: August 2020

AbstractGranulocyte and monocyte adsorption apheresis (GMA) is usually performed weekly (consisting of five sessions) for refractory skin diseases, such as generalized pustular psoriasis (GPP). The time to remission of inflammatory bowel diseases has been reported to be significantly shorter in intensive GMA (twice a week) than in regular GMA (once a week). Despite several reports of GPP cases treated with intensive GMA, the efficacy of intensive GMA has not been verified in GPP. Herein, we present two GPP patients with a mutation in theIL36RNgene, who initially received regular GMA, and intensive GMA upon recurrence. There were no adverse effects during regular and intensive GMA for both patients. Because concomitant medication was only prednisolone (20 mg/day) during regular and intensive GMA, intensive GMA showed superiority to regular GMA in patient 1. Although concomitant medications were different between regular and intensive GMA in patient 2, these drugs had been used before the start of each GMA therapy. We cannot neglect the effects of concomitant drugs, but we observed a shorter time to remission in intensive GMA than that in regular GMA in both patients. More case studies will be necessary for evaluating the clinical efficacy of intensive GMA.
Longer photoperiods through range shifts and artificial light lead to a destabilizing increase in host–parasitoid interaction strength
Authors: Kehoe Rachel , Sanders Dirk , Cruse Dave , Silk Matthew , Gaston Kevin J. , Bridle Jon R. , van Veen Frank 
Published: August 2020

Abstract

Many organisms are experiencing changing daily light regimes due to latitudinal range shifts driven by climate change and increased artificial light at night (ALAN). Activity patterns are often driven by light cycles, which will have important consequences for species interactions.

We tested whether longer photoperiods lead to higher parasitism rates by a day‐active parasitoid on its host using a laboratory experiment in which we independently varied daylength and the presence of ALAN. We then tested whether reduced nighttime temperature tempers the effect of ALAN.

We found that parasitism rate increased with daylength, with ALAN intensifying this effect only when the temperature was not reduced at night. The impact of ALAN was more pronounced under short daylength. Increased parasitoid activity was not compensated for by reduced life span, indicating that increased daylength leads to an increase in total parasitism effects on fitness.

To test the significance of increased parasitism rate for population dynamics, we developed a host–parasitoid model. The results of the model predicted an increase in time‐to‐equilibrium with increased daylength and, crucially, a threshold daylength above which interactions are unstable, leading to local extinctions.

Here we demonstrate that ALAN impact interacts with daylength and temperature by changing the interaction strength between a common day‐active consumer species and its host in a predictable way. Our results further suggest that range expansion or ALAN‐induced changes in light regimes experienced by insects and their natural enemies will result in unstable dynamics beyond key tipping points in daylength.
Comparison of chitin‐induced natural transformation in pandemic Vibrio choleraeO1 El Tor strains
Authors: Stutzmann Sandrine , Blokesch Melanie 
Published: August 2020

SummaryThe human pathogen Vibrio cholerae serves as a model organism for many important processes ranging from pathogenesis to natural transformation, which has been extensively studied in this bacterium. Previous work has deciphered important regulatory circuits involved in natural competence induction as well as mechanistic details related to its DNA acquisition and uptake potential. However, since competence was first reported for V. cholerae in 2005, many researchers have struggled with reproducibility in certain strains. In this study, we therefore compare prominent seventh pandemic V. cholerae isolates, namely strains A1552, N16961, C6706, C6709, E7946, P27459, and the close relative MO10, for their natural transformability and decipher underlying defects that mask the high degree of competence conservation. Through a combination of experimental approaches and comparative genomics based on new whole‐genome sequences and de novo assemblies, we identify several strain‐specific defects, mostly in genes that encode key players in quorum sensing. Moreover, we provide evidence that most of these deficiencies might have recently occurred through laboratory domestication events or through the acquisition of mobile genetic elements. Lastly, we highlight that differing experimental approaches between research groups might explain more of the variations than strain‐specific alterations.
Transactive Teaching in a Time of Climate Crisis
Authors: Säfström Carl Anders , Östman Leif 
Published: August 2020

Abstract
This article discusses three problems that need to be tackled when the climate crisis becomes ‘a sustainability issue’ to be taught in schools. The article highlights, first, how knowledge concerning sustainability in schools risks being reduced and made into knowledge about ‘things’. Secondly, it also discusses how students in such a context risk being treated as instruments for ways of being in the world, rather than being subjects with ethical and political concerns for the world in which they live ‘here and now’. Thirdly, as we explore through some empirical examples, such reduction and instrumentalism objectifies both students and nature, which makes an adequate response to the crises obsolete. As an alternative, the article develops a notion of grievability and its importance for adequately responding to all living beings within a project of sustainability. To this end, it develops suggestions for a transactive teaching approach in a time of climate crisis.
Stepwise student migration: A trajectory analysis of Iranians moving from Turkey to Europe and North America
Authors: Zijlstra Judith 
Published: August 2020

AbstractIn the last decade, political and economic constraints have prompted many students to leave Iran. While Europe and North America have traditionally been Iranians' preferred destinations, selective entry procedures make direct access increasingly difficult. This article focuses on Iranian students' stepwise migration strategies to reach Western countries through Turkey. My research indicates that stepwise migration theory can be applied to international students, as visa restrictions and the selectivity of Western universities transformed Turkey into a stepwise migration corridor. The article also considers the advantages of the trajectory analysis method I developed. Trajectory analysis is a longitudinal and mobile method whereby migrants are followed over time and space. It enables the researcher to compare data about migrants who move stepwise and those who move crosswise by staying in Turkey. The research is based on interviews with 36 Iranians in Turkey, Europe, and the United States, of whom 15 moved in stepwise fashion. An important outcome is that students' academic capital is a crucial indicator for their ability to migrate to the West. This finding points to path dependency in students' trajectories along a hierarchy of destinations: not only in geographical terms but also in terms of the perceived level of educational institutions' reputations.
Effect of isochoric freezing on quality aspects of minimally processed potatoes
Authors: Bilbao‐Sainz Cristina , Zhao Yuanheng , Takeoka Gary , Williams Tina , Wood Delilah , Chiou Bor‐Sen , Powell‐Palm Matthew J. , Wu Vivian C.H. , Rubinsky Boris , McHugh Tara 
Published: August 2020

AbstractThe enhanced interest in greater convenience foods has recently led to the expansion of minimally processed potato products. This study investigated the effects of isochoric freezing on pre‐peeled potato cubes, including quality attributes (microstructure, texture, and color), nutritional value (ascorbic acid (AA) content, total phenolic content, and antioxidant capacity), and polyphenol oxidase activity. Isochoric freezing (−3 °C/30 MPa) was compared with isobaric freezing (−3 °C/0.1 MPa) and individual quick freezing followed by frozen storage at −20 °C for 4 weeks. The isochoric sample had lower drip loss and volume shrinkage as well as better preserved texture and microstructure than the other samples. All freezing methods caused an increase in total phenolic content and antioxidant capacity, but a decrease in AA content. Also, all freezing methods caused browning of the thawed potatoes, but isochoric freezing delayed its onset for more than 1 week.Practical ApplicationResults showed that isochoric freezing of pre‐peeled and cut potatoes caused less freeze damage than isobaric and individual quick freezing, which might find application in the commercial preservation of minimally processed food products.
A protocol for the large‐scale analysis of reefs using Structure from Motion photogrammetry
Authors: Bayley Daniel T. I. , Mogg Andrew O. M. 
Published: August 2020

Abstract

Substrate complexity is an essential metric of reef health and a strong predictor of several ecological processes connected to the reef, including disturbance, resilience, and associated community abundance and diversity.

Underwater Structure from Motion (SfM) photogrammetry has been growing rapidly in use over the last 5 years due to advances in computing power, reduced costs of underwater digital cameras and a push for reproducible data. This has led to the adaptation of an originally terrestrial survey technique into the marine realm, which can now be applied at the habitat scale.

This technique allows researchers to make detailed 3D reconstructions of reef surfaces for morphometric analysis of reef physical structure and perform large‐scale image‐mosaic mapping. SfM is useful for both reef‐scale and colony‐scale assessments, where visual or acoustic methods are impractical or not sufficiently detailed.

Here we provide a protocol for the collection, analysis and display of 3D reef data, focussing on large‐scale habitat assessments of coral reefs using primarily open‐source software. We further suggest applications for other underwater environments and scales of assessment, and hope this standardized protocol will help researchers apply this technology and inspire new avenues of ecological research.
The dawn of a new synthetic opioid era: the need for innovative interventions
Authors: Pardo Bryce , Taylor Jirka , Caulkins Jon , Reuter Peter , Kilmer Beau 
Published: September 2020

AbstractBackgroundOverdose deaths related to illegal drugs in North American markets are now dominated by potent synthetic opioids such as fentanyl, a circumstance foreshadowed by often‐overlooked events in Estonia since the turn of the century. Market transitions generate important and far‐reaching implications for drug policy.Argument and analysisThe supplier‐driven introduction of illegally manufactured synthetic opioids into street opioids is elevating the risk of fatal overdose. Using the most recent overdose mortality and drug seizure data in North America, we find that overdose deaths and seizures involving synthetic opioids are geographically concentrated, but this might be changing. Examination here suggests that in some places fentanyl and its analogues have virtually displaced traditional opioids, such as heroin. The concealing of synthetic opioids in powders sold as heroin or pressed into counterfeit medications substantially increases harms. The nature and scale of the challenge posed by synthetic opioids is unprecedented in recent drug policy history.ConclusionsThere is urgent need for policy and technological innovation to meet the challenges posed by illegally produced synthetic opioids. Novel interventions worth examining include supervising drug use, proactively deterring on‐line distribution and new technologies aimed at improving transparency, such as point‐of‐use drug content testing. Continuing to approach this problem only with existing policies and available methods, such as naloxone, is unlikely to be enough and will result in many premature deaths.