bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasticity of cold hardiness in the eastern spruce budworm,Choristoneura fumiferana
Authors: Butterson Skye , Roe Amanda D. , Marshall Katie E. 
Published: April 2021

AbstractHigh latitude insect populations must cope with extreme conditions, particularly cold temperatures. Insects use a variety of cold hardiness mechanisms to withstand this temperature stress, and these can drive geographic distributions through overwintering mortality. The degree of cold hardiness can be altered by two evolved responses: phenotypic plasticity and local adaptation. Phenotypic plasticity can occur within or between generations (transgenerational plasticity; TGP), and local adaptation can evolve through directional selection in response to regional climatic differences. We used the eastern spruce budworm,Choristoneura fumiferana(Lepidoptera: Tortricidae) as a model to explore the role that variable winter temperatures play in inducing two aspects of plasticity in cold hardiness: TGP and local adaptation in phenotypic plasticity. This species is one of the most destructive boreal forest pests in North America, therefore accurately predicting overwintering survival is essential for effective management. While we found no evidence of TGP in cold hardiness, there was a long-term fitness cost to larvae that experienced repeated cold exposures. We also found evidence of local adaptation in both seasonal and short-term plasticity of cold hardiness. These findings provide evidence for the importance of phenotypic plasticity and local adaptation when modelling species distributions.
Evidence or Confidence: What is really monitored during a decision?
Authors: Lee Douglas G. , Daunizeau Jean , Pezzulo Giovanni 
Published: April 2021

AbstractAssessing our confidence in the choices we make is of paramount importance to making adaptive decisions, and it is thus no surprise that we excel in this ability. However, standard models of decision-making, such as the drift-diffusion model (DDM), treat confidence assessment as a post-hoc or parallel process that does not directly influence the choice, which depends only on accumulated evidence. Here, we pursue the alternative hypothesis that what is monitored during a decision is an evolving sense of confidence (that the to-be-selected option is the best) rather than raw evidence. Monitoring confidence has the appealing consequence that the decision threshold corresponds to a desired level of confidence for the choice, and that confidence improvements can be traded off against the resources required to secure them. We show that most previous findings on perceptual and value-based decisions traditionally interpreted from anevidence-accumulationperspective can be explained more parsimoniously from our novelconfidence-drivenperspective. Furthermore, we show that our novelconfidence-driven DDM(cDDM) naturally generalizes to decisions involving any number of alternative options – which is notoriously extemporaneous using traditional DDM or related models. Finally, we discuss future empirical evidence that could be useful in adjudicating between these alternatives.
Selective functional inhibition of a tumor-derived p53 mutant by cytosolic chaperones identified using split-YFP in budding yeast
Authors: Denney Ashley S. , Weems Andrew D. , McMurray Michael A. 
Published: April 2021

ABSTRACTLife requires the oligomerization of individual proteins into higher-order assemblies. In order to form functional oligomers, monomers must adopt appropriate three-dimensional structures. Molecular chaperones transiently bind nascent or misfolded proteins to promote proper folding. Single missense mutations frequently cause disease by perturbing folding despite chaperone engagement. A misfolded mutant capable of oligomerizing with wild-type proteins can dominantly poison oligomer function. We previously found evidence that human-disease-linked mutations inSaccharomyces cerevisiaeseptin proteins slow folding and attract chaperones, resulting in a kinetic delay in oligomerization that prevents the mutant from interfering with wild-type function. Here we build upon our septin studies to develop a new approach to identifying chaperone interactions in living cells, and use it to expand our understanding of chaperone involvement, kinetic folding delays, and oligomerization in the recessive behavior of tumor-derived mutants of the tumor suppressor p53. We find evidence of increased binding of several cytosolic chaperones to a recessive, misfolding-prone mutant, p53(V272M). Similar to our septin results, chaperone overexpression inhibits the function of p53(V272M) with minimal effect on the wild type. Unlike mutant septins, p53(V272M) is not kinetically delayed under conditions in which it is functional. Instead, it interacts with wild-type p53 but this interaction is temperature sensitive. At high temperatures or upon chaperone overexpression, p53(V272M) is excluded from the nucleus and cannot function or perturb wild-type function. Chaperone inhibition liberates the mutant to enter the nucleus where it has a slight dominant-negative effect. These findings provide new insights into the effects of missense mutations.
Reconstructing SNP Allele and Genotype Frequencies from GWAS Summary Statistics
Authors: Yang Zhiyu , Paschou Peristera , Drineas Petros 
Published: April 2021

AbstractThe emergence of genomewide association studies (GWAS) has led to the creation of large repositories of human genetic variation, creating enormous opportunities for genetic research and worldwide collaboration. Methods that are based on GWAS summary statistics seek to leverage such records, overcoming barriers that often exist in individual-level data access while also offering significant computational savings. Here, we propose a novel framework that can reconstruct allelic and genotypic counts/frequencies for each SNP from case-control GWAS summary statistics. Our framework is simple and efficient without the need of any complicated underlying assumptions. Illustrating the great potential of this framework we also propose three summary-statistics-based applications implemented in a new software package (ReACt): GWAS meta-analysis (with and without sample overlap), case-case GWAS, and, for the first time, group polygenic risk score (PRS) estimation. We evaluate our methods against the current state-of-the-art on both synthetic data and real genotype data and show high performance in power and error control. Our novel group PRS method based on summary statistics could not be achieved prior to our proposed framework. We demonstrate here the potential applications and advantages of this approach. Our work further highlights the great potential of summary-statistics-based methodologies towards elucidating the genetic background of complex disease and opens up new avenues for research.
Herbaceous production lost to tree encroachment in United States rangelands
Authors: Morford Scott L. , Allred Brady W. , Twidwell Dirac , Jones Matthew O. , Maestas Jeremy D. , Roberts Caleb P. , Naugle David E. 
Published: April 2021

AbstractRangelands of the United States provide ecosystem services that benefit society and rural economies. Native tree encroachment is often overlooked as a primary threat to rangelands due to the slow pace of tree cover expansion and the positive public perception of trees. Still, tree encroachment fragments these landscapes and reduces herbaceous production, thereby threatening habitat quality for grassland wildlife and the economic sustainability of animal agriculture.Recent innovations in satellite remote sensing permit the tracking of tree encroachment and the corresponding impact on herbaceous production. We analyzed tree cover change and herbaceous production across the western United States from 1990 to 2019.We show that tree encroachment is widespread in U.S. rangelands; absolute tree cover has increased by 50% (77,323 km2) over 30 years, with more than 25% (684,852 km2) of U.S. rangeland area experiencing tree cover expansion. Since 1990, 302 ± 30 Tg of herbaceous biomass have been lost. Accounting for variability in livestock biomass utilization and forage value reveals that this lost production is valued at between $4.1 - $5.6 billion U.S. dollars.Synthesis and applications: The magnitude of impact of tree encroachment on rangeland loss is similar to conversion to cropland, another well-known and primary mechanism of rangeland loss in the U.S. Prioritizing conservation efforts to prevent tree encroachment can bolster ecosystem and economic sustainability, particularly among privately-owned lands threatened by land-use conversion.
The chromatin remodeler Ino80 mediates alternative RNAPII pausing site determination
Authors: Cheon Youngseo , Han Sungwook , Kim Taemook , Lee Daeyoup 
Published: April 2021

AbstractPromoter-proximal pausing of RNA polymerase II (RNAPII) is a critical step in early transcription elongation for the precise regulation of gene expression. Here, we provide evidence of promoter-proximal pausing-like distributions of RNAPII inS. cerevisiae. We found that genes bearing an alternative pausing site utilize Ino80p to properly localize RNAPII pausing at the first pausing site and to suppress the accumulation of RNAPII at the second pausing site, which is tightly associated with the +1 nucleosome. This alternative pausing site determination was dependent on the remodeling activity of Ino80p to modulate the +1 nucleosome position and might be controlled synergistically with Spt4p. Furthermore, we observed similar Ino80-dependent RNAPII pausing in mouse embryonic stem cells (mESCs). Based on our collective results, we hypothesize that the chromatin remodeler Ino80 plays a highly conserved role in regulating early RNAPII elongation to establish intact pausing.
First-principles model of optimal translation factors stoichiometry
Authors: Lalanne Jean-Benoît , Li Gene-Wei 
Published: April 2021

AbstractEnzymatic pathways have evolved uniquely preferred protein expression stoichiometry in living cells, but our ability to predict the optimal abundances from basic properties remains underdeveloped. Here we report a biophysical, first-principles model of growth optimization for core mRNA translation, a multi-enzyme system that involves proteins with a broadly conserved stoichiometry spanning two orders of magnitude. We show that a parsimonious flux model constrained by proteome allocation is sufficient to predict the conserved ratios of translation factors through maximization of ribosome usage The analytical solutions, without free parameters, provide an interpretable framework for the observed hierarchy of expression levels based on simple biophysical properties, such as diffusion constants and protein sizes. Our results provide an intuitive and quantitative understanding for the construction of a central process of life, as well as a path toward rational design of pathway-specific enzyme expression stoichiometry.
Re-investigating the coughing rat model of pertussis to understandBordetella pertussispathogenesis
Authors: Hall Jesse M. , Kang Jason , Kenney Sophia M. , Wong Ting Y. , Bitzer Graham J. , Kelly Claire O. , Kisamore Caleb A. , Boehm Dylan T. , DeJong Megan A. , Wolf M. Allison , Sen-Kilic Emel , Horspool Alexander M. , Bevere Justin R , Barbier Mariette , Damron F. Heath 
Published: April 2021

AbstractBordetella pertussis(Bp) is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP; DTaP; Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the re-emergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. Emergence of genetically diverging strains combined with waning aP vaccine efficacy call for re-evaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged seven-week-old Sprague-Dawley rats with 108viable Tohama 1 and D420 and measured the hallmark signs/symptoms ofBpinfection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole body plethysmography. Onset of cough occurred between 2-4 days afterBpchallenge averaging five coughs per fifteen minutes, with peak coughing occurring at day eight post infection averaging upward of thirteen coughs per fifteen minutes. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days post challenge. The rats exhibited increased bronchial restriction followingBpinfection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti-BpIgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences betweenBpstrains.
Litter commensal bacteria can limit the horizontal gene transfer of antimicrobial resistance toSalmonellain chickens
Authors: Oladeinde Adelumola , Abdo Zaid , Zwirzitz Benjamin , Woyda Reed , Lakin Steven M. , Press Maximilian O. , Cox Nelson A. , Thomas Jesse C. , Looft Torey , Rothrock Michael J. , Zock Gregory , Lawrence Jodie Plumblee , Cudnik Denice , Ritz Casey , Aggrey Samuel E. , Liachko Ivan , Grove Jonas R. , Wiersma Crystal 
Published: April 2021

AbstractFostering a ’balanced’ gut microbiome through the administration of beneficial microbes that can competitively exclude pathogens has gained a lot of attention and use in human and animal medicine. However, little is known about how microbes affect the horizontal gene transfer of antimicrobial resistance (AMR). To shed more light on this question, we challenged neonatal broiler chicks raised on reused broiler chicken litter – a complex environment made up of decomposing pine shavings, feces, uric acid, feathers, and feed, withSalmonellaHeidelberg (S. Heidelberg), a model pathogen. Neonatal chicks challenged withS. Heidelberg and raised on reused litter were more resistant toS. Heidelberg cecal colonization than chicks grown on fresh litter. Furthermore, chicks grown on reused litter were at a lower risk of colonization withS. Heidelberg strains that encoded AMR on IncI1 plasmids. We used 16S rRNA gene sequencing and shotgun metagenomics to show that the major difference between chicks grown on fresh litter and reused litter was the microbiome harbored in the litter and ceca. The microbiome of reused litter samples was more uniform and enriched in functional pathways related to the biosynthesis of organic and antimicrobial molecules than fresh litter samples. We found thatE. coliwas the main reservoir of plasmids encoding AMR and that the IncI1 plasmid was maintained at a significantly lower copy per cell in reused litter compared to fresh litter. These findings support the notion that commensal bacteria play an integral role in the horizontal transfer of plasmids encoding AMR to pathogens likeSalmonella.Importance/SignificanceAntimicrobial resistance spread is a worldwide health challenge, stemming in large part, from the ability of microorganisms to share their genetic material through horizontal gene transfer. To address this issue, many countries and international organization have adopted a One health approach to curtail the proliferation of antimicrobial resistant bacteria. This includes the removal and reduction of antibiotics used in food animal production and the development of alternatives to antibiotics. However, there is still a significant knowledge gap in our understanding of how resistance spreads in the absence of antibiotic selection and the role commensal bacteria play in reducing antibiotic resistance transfer. In this study, we show that commensal bacteria play a key role in reducing the horizontal gene transfer of antibiotic resistance toSalmonellaand provide the identity of the bacterial species that potentially perform this function in broiler chickens and also postulate the mechanism involved.
Early embryonic loss following intravaginal Zika virus challenge in rhesus macaques
Authors: Newman Christina M. , Tarantal Alice F. , Martinez Michele L. , Simmons Heather A. , Morgan Terry K. , Zeng Xiankun , Rosinski Jenna R. , Bliss Mason I. , Bohm Ellie K. , Dudley Dawn M. , Aliota Matthew T. , Friedrich Thomas C. , Miller Christopher J. , O’Connor David H. 
Published: April 2021

AbstractZika virus (ZIKV) is an arthropod-borne virus (arbovirus) and is primarily transmitted byAedesspecies mosquitoes; however, ZIKV can also be sexually transmitted. During the initial epidemic and in places where ZIKV is now considered endemic, it is difficult to disentangle the risks and contributions of sexual versus vector-borne transmission to adverse pregnancy outcomes. To examine the potential impact of sexual transmission of ZIKV on pregnancy outcome, we challenged three rhesus macaques (Macaca mulatta) three times intravaginally with 1 × 107PFU of a low passage, African lineage ZIKV isolate (ZIKV-DAK) in the first trimester (∼30 days gestational age). Samples were collected from all animals initially on days 3 through 10 post challenge, followed by twice, and then once weekly sample collection; ultrasound examinations were performed every 3-4 days then weekly as pregnancies progressed. All three dams had ZIKV RNA detectable in plasma on day 3 post-ZIKV challenge. At approximately 45 days gestation (17-18 days post-challenge), two of the three dams were found to have nonviable embryos by ultrasound. Viral RNA was detected in recovered tissues and at the maternal-fetal interface (MFI) in both cases. The remaining viable pregnancy proceeded to near term (∼155 days gestational age) and ZIKV RNA was detected at the MFI but not in fetal tissues. These results suggest that sexual transmission of ZIKV may represent an underappreciated risk of pregnancy loss during early gestation.
Differentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory
Authors: Tonnerre Pierre , Wolski David , Subudhi Sonu , Al-Jabban Jihad , Hoogeveen Ruben C. , Damasio Marcos , Drescher Hannah K. , Bartsch Lea M. , Tully Damien C. , Sen Debattama R. , Bean David J. , Brown Joelle , Torres-Cornejo Almudena , Robidoux Maxwell , Kvistad Daniel , Alatrakchi Nadia , Cui Ang , Lieb David , Cheney James A. , Gustafson Jenna , Lewis-Ximenez Lia L , Massenet-Regad Lucile , Eisenhaure Thomas , Aneja Jasneet , Haining W. Nicholas , Chung Raymond T. , Hacohen Nir , Allen Todd M. , Kim Arthur Y. , Lauer Georg M. 
Published: April 2021

AbstractT cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Analysis of antigen-specific CD8+ T cells before and after antigen removal in human hepatitis C virus (HCV) infection confirmed pervasive phenotypic, functional, and transcriptional differences between exhausted and memory CD8+ T cells. After viral cure, we observed broad phenotypic and transcriptional changes in clonally stable exhausted T-cell populations suggesting differentiation towards a memory-like profile. However, functionally, the cells showed little improvement and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for shorter periods of time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved acute HCV infection. Thus, duration of T cell stimulation impacts the ability to recover from exhaustion, as antigen removal after long-term T cell exhaustion is insufficient for the development of key T cell memory characteristics.
Pupil diameter tracked during motor adaptation in humans
Authors: Yokoi Atsushi , Weiler Jeffrey 
Published: April 2021

AbstractPupil diameter, under constant illumination, is known to reflect individuals’ internal states, such as surprise about observation and environmental uncertainty. Despite the growing use of pupillometry in cognitive learning studies as an additional measure for examining internal states, few studies have used pupillometry in human motor learning studies. Here we provide the first detailed characterization of pupil diameter changes in a short-term reach adaptation paradigm. We measured pupil changes in 91 human participants while they adapted to abrupt, gradual, or switching force field conditions. Sudden increases in movement error caused by the introduction/reversal of the force field resulted in strong phasic pupil dilation during movement accompanied by a transient increase in tonic pre-movement baseline pupil diameter in subsequent trials. In contrast, clear changes in pupil responses were absent when the force field was gradually introduced, indicating that error drove the changes in pupil responses. Nevertheless, we found an association between baseline pupil diameter and awareness of the gradually-introduced perturbation assessed post-experimentally. In all experiments, we also found a strong co-occurrence of larger baseline pupil diameter and slower reaction and movement time after each set break. Interestingly, error-induced pupil responses gradually became insensitive after experiencing multiple reversals. Collectively, these results suggest that tonic baseline pupil diameter reflects one’s belief about environmental uncertainty, whereas phasic pupil dilation during movement reflects surprise about a sensory outcome (i.e., movement error), and both effects are modulated by novelty. Our results provide a new approach for non-verbally assessing participants’ internal states during motor learning.
Transport of Ketoprofen in Mammalian Blood Plasma
Authors: Czub Mateusz P. , Shabalin Ivan G. , Minor Wladek 
Published: April 2021

SummaryKetoprofen is a popular non-steroidal anti-inflammatory drug (NSAID) transported in the bloodstream mainly by serum albumin (SA). Ketoprofen is known to have multiple side effects and interactions with hundreds of other drugs, which might be related to its vascular transport by SA. Our work reveals that ketoprofen binds to a different subset of drug binding sites on human SA than has been observed for other species, despite the conservation of drug sites between species. We discuss potential reasons for the observed differences in the drug’s preferences for particular sites, including ketoprofen binding determinants in mammalian SAs and the effect of fatty acids on drug binding. The presented results show that the SA drug sites to which a particular drug binds cannot be easily predicted based only on a complex of SA from another species and the conservation of drug sites between species.