bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-Benefit Analysis of a Distracted Pedestrian Intervention
Authors: Rahim Md Jillur , Schwebel David C. , Hasan Ragib , Griffin Russell , Sen Bisakha 
Published: August 2022

ABSTRACTObjectiveCellphone ubiquity has increased distracted pedestrian behavior and contributed to growing pedestrian injury rates. A major barrier to large-scale implementation of prevention programs is unavailable information on potential net monetary benefits. We evaluated net economic benefits of StreetBit, a program that reduces distracted pedestrian behavior by sending warnings from intersection-installed Bluetooth beacons to distracted pedestrians’ smartphones.MethodsThree data sources were used: (1) fatal, severe, non-severe pedestrian injury rates from Alabama’s electronic crash-reporting-system; (2) expected costs per fatal, severe, non-severe pedestrian injury – including medical cost, value of statistical life, work-loss cost, quality-of-life cost – from CDC; and (3) prevalence of distracted walking from extant literature. We computed and compared estimated monetary costs of distracted walking in Alabama and monetary benefits from implementing StreetBit to reduce pedestrian injuries at intersections.ResultsOver 2019-2021, Alabama recorded an annual average of 31 fatal, 83 severe, and 115 non-severe pedestrian injuries in intersections. Expected costs/injury were $11 million, $339,535, and $93,877, respectively. The estimated range of distracted walking prevalence is 25%-40%, and StreetBit demonstrates 19.1% (95%CI: 1.6%-36.0%) reduction. These figures demonstrate potential annual cost savings from using interventions like StreetBit statewide ranging from $18.1-$29 million. Potential costs range from $3,208,600 (beacons at every-fourth urban intersection) to $6,359,200 (every other intersection).ConclusionsEven under the most parsimonious scenario (25% distracted pedestrians; densest beacon placement), StreetBit yields $11.8 million estimated net annual benefit. Existing data sources can be leveraged to predict net monetary benefits of distracted pedestrian interventions like StreetBit and facilitate large-scale intervention adoption.SUMMARYWhat is already known in this topicSmartphone-related distraction is a likely contributing factor to the increasing rate of pedestrian fatalities and injuries in the US. However, interventions to reduce pedestrian distraction have not been widely adapted.What this study addsOne barrier to widespread adaption is lack of information on benefits versus costs. This study examines the economic costs and benefits of an intervention that reduces distracted walking to increase pedestrian safety, and provides a template showing how existing data sources can be leveraged to do similar analyses for other interventions designed to reduce pedestrian safety.How this study might affect research, practice or policyThe template developed in this study can facilitate large-scale implementation of any intervention designed to prevent pedestrian fatalities and injuries by providing policymakers information on net benefits of the intervention.
Syncytial nerve net in a ctenophore sheds new light on the early evolution of nervous systems
Authors: Burkhardt Pawel , Medhus Astrid , Digel Leonid , Naumann Benjamin , Soto-Àngel Joan J , Nordmann Eva-Lena , Sachkova Maria Y , Kittelmann Maike 
Published: August 2022

SummaryA fundamental breakthrough in neurobiology has been the formulation of the neuron doctrine by Santiago Ramón y Cajal, which states that the nervous system is composed of discrete individual cells. Electron microscopy later confirmed the doctrine and allowed the identification of synaptic connections. Here we use volume electron microscopy and 3D reconstructions to characterize the nerve net of a cydippid-phase ctenophore, belonging to one of the earliest-branching animal lineages. We found that neurons of its subepithelial nerve net do not follow Cajal’s neuron doctrine but instead show a continuous plasma membrane forming a syncytium. This is more similar to the reticulate theory of the nervous system put forward by Camillo Golgi. Additionally, we were able to identify new sensory cell types and describe simple neuro-sensory circuits for cydippid-phase ctenophores. Together with the ctenophore-specific synaptic architecture and the presence of an extensive repertoire of lineage-specific neuropeptides our morphological data provide substantial evidence for the independent evolution of the nervous system of ctenophores and the remaining animals.
Local RNA Structure, Ion Hydration Shell and the Energy Barrier for Water Exchange from the Ion Hydration Shell Determine the Mechanism of Ion Condensation on Specific RNA Sites
Authors: Halder Antarip , Kumar Sunil , Habibullah Sk , Reddy Govardhan 
Published: August 2022

AbstractRNA folding and functioning require the binding of metal ions in specific cavities of the folded structure. This property is critical to the functioning of riboswitches that especially regulate the metal ions concentration in bacteria. However, the fundamental principles governing the specific binding of metal ions in RNA are unclear. We probed the condensation mechanism of biologically relevant alkali (Na+ and K+), alkaline earth (Mg2+ and Ca2+), and transition metals (Mn2+, Co2+, Ni2+ and Zn2+) on a part of the Ni2+ and Co2+ (NiCo) sensing riboswitch aptamer domain using computer simulations. The selected structure has multiple secondary structural elements and a single site for the specific binding of a metal ion. We show that three factors primarily determine the binding of a metal ion to an RNA site - (1) The varying structural constraints from different RNA secondary structural elements strongly influence the metal ion binding. The mode of ion binding depends on the local structure around the RNA’s ion-binding pocket. (2) The arrangement of water molecules in the ion hydration shell, and (3) the energy barrier for the ion to lose a water molecule from its hydration shell and transition from an outer to an inner shell interaction, which is primarily influenced by the metal ion charge density. These results have implications for designing biocompatible sensors using riboswitches to probe the concentration of intracellular metal ions.
Disease decreases variation in host community structure in an old-field grassland
Authors: Grunberg Rita L. , Halliday Fletcher W. , Heckman Robert W. , Joyner Brooklynn N. , O’Keeffe Kayleigh R. , Mitchell Charles E. 
Published: August 2022

AbstractDisease may modulate variation in host community structure by modifying the interplay of deterministic and stochastic processes. For instance, deterministic processes like ecological selection can benefit species less impacted by disease. When disease consistently selects for certain host species, this can reduce variation in host community composition. On the other hand, when host communities are less impacted by disease and selection is weaker, stochastic processes (e.g., drift, dispersal) may play a bigger role in host community structure, which can increase variation in structure among communities. While effects of disease on host community structure have been quantified in field experiments, few have addressed the role of disease in modulating variation in structure among host communities. To address this, we conducted a field experiment spanning three years, using a tractable system: foliar fungal pathogens in an old-field grassland community dominated by the grassLolium arundinaceum, tall fescue. We reduced foliar fungal disease burden in replicate host communities (experimental plots in intact vegetation) in three fungicide regimens that varied in the duration of fungicide exposure and included a fungicide-free control. We measured host diversity, biomass, and variation in community structure among replicate communities. Disease reduction generally decreased plant richness and increased aboveground biomass relative to communities experiencing ambient levels of disease. Despite changes in structure of the plant communities over the experiment’s three years, the effects of disease reduction on plant richness and biomass were consistent across years. However, disease reduction did not reduce variation in host community structure, providing little evidence for ecological selection by competition or other deterministic processes. Instead, disease reduction tended to amplify variation in host community structure among replicate communities (i.e., within fungicide treatment groups), suggesting that disease diminished the degree to which host communities were structured by stochastic processes. These results of experimental disease reduction both highlight the potential importance of stochastic processes in plant communities and reveal the potential for disease to regulate variation in host community structure.
Deep Learning-based Phenotype Imputation on Population-scale Biobank Data Increases Genetic Discoveries
Authors: An Ulzee , Pazokitoroudi Ali , Alvarez Marcus , Huang Lianyun , Bacanu Silviu , Schork Andrew J. , Kendler Kenneth , Pajukanta Päivi , Flint Jonathan , Zaitlen Noah , Cai Na , Dahl Andy , Sankararaman Sriram 
Published: August 2022

AbstractBiobanks that collect deep phenotypic and genomic data across large numbers of individuals have emerged as a key resource for human genetic research. However, phenotypes acquired as part of Biobanks are often missing across many individuals, limiting the utility of these datasets. The ability to accurately impute or “fill-in” missing phenotypes is critical to harness the power of population-scale Biobank datasets. We propose AutoComplete, a deep learning-based imputation method which can accurately impute missing phenotypes in population-scale Biobank datasets. When applied to collections of phenotypes measured across ≈ 300K individuals from the UK Biobank, AutoComplete improved imputation accuracy over existing 2 methods (average improvement in r2 of 18% for all phenotypes and 42% for binary phenotypes). We explored the utility of phenotype imputation for improving the power of genome-wide association studies (GWAS) by applying our method to a group of five clinically relevant traits with an average missigness rate of 83% (67% to 94%) leading to an an increase in effective sample size of ≈2-fold on average (0.5 to 3.3-fold across the phenotypes). GWAS on the resulting imputed phenotypes led to an increase in the total number of loci significantly associated to the traits from four to 129. Our results demonstrate the utility of deep-learning based imputation to increase power for genetic discoveries in existing biobank data sets.
The IgHEμ-MAR regions promote UNG-dependent error-prone repair to optimize somatic hypermutation
Authors: Martin Ophélie , Thomas Morgane , Marquet Marie , Garot Armand , Brousse Mylène , Bender Sébastien , Carrion Claire , Choi Jee Eun , Vuong Bao Q. , Gearhart Patricia J. , Maul Robert W. , Noir Sandrine Le , Pinaud Eric 
Published: August 2022

AbstractTwo scaffold/matrix attachment regions (5’- and 3’-MARsEμ) flank the intronic core enhancer (cEμ) within the immunoglobulin heavy chain locus (IgH). Besides their conservation in mice and humans, the physiological role ofMARsEμis still unclear and their involvement in somatic hypermutation (SHM) has never been deeply evaluated. By analysing a mouse model devoid ofMARsEμ, we observed an inverted substitution pattern: SHM being decreased upstream fromcEμand increased downstream of it. Strikingly, the SHM defect induced byMARsEμ-deletion was accompanied by an increase of sense transcription of the IgH V region, excluding a direct transcription-coupled effect. Interestingly, by breeding to DNA repair-deficient backgrounds, we showed that the SHM defect, observed upstream fromcEμin this model, was not due to a decrease in AID deamination but rather the consequence of a defect in base excision repair-associated unfaithful repair process. Our study pointed out an unexpected “fence” function ofMARsEμregions in limiting the error-prone repair machinery to the variable region of Ig gene loci.
A synthetic genetic array screen for interactions with the RNA helicase DED1 during cell stress in budding yeast
Authors: Carey Sara B. , List Hannah M. , Siby Ashwin , Guerra Paolo , Bolger Timothy A. 
Published: August 2022

AbstractDuring cellular stress it is essential for cells to alter their gene expression to adapt and survive. Gene expression is regulated at multiple levels, but translation regulation is both a method for rapid changes to the proteome and, as one of the most energy-intensive cellular processes, a way to efficiently re-direct cellular resources during stress conditions. Despite this ideal positioning, many of the specifics of how translation is regulated, positively or negatively, during various types of cellular stress remain poorly understood. To further assess this regulation, we examined the essential translation factor Ded1, an RNA helicase that has been previously shown to play important roles in the translational response to cellular stress. In particular, ded1 mutants display an increased resistance to growth inhibition and translation repression induced by the TOR pathway inhibitor, rapamycin, suggesting that normal stress responses are partially defective in these mutants. To gain further insight into Ded1 translational regulation during stress, synthetic genetic array analysis was conducted in the presence of rapamycin with a ded1 mutant and a library of non-essential genes in S. cerevisiae to identify positive and negative genetic interactions in an unbiased manner. Here we report the results of this screen and subsequent network mapping and GO-term analysis. Hundreds of candidate interactions were identified, which fell into expected categories, such as ribosomal proteins and amino acid biosynthesis, as well as unexpected ones, including membrane trafficking, sporulation, and protein glycosylation. Therefore, these results provide several specific directions for further comprehensive studies.
The circulating phageome reflects bacterial infections
Authors: Haddock NL , Barkal LJ , Ram-Mohan N , Kaber G , Chiu CY , Bhatt AS , Yang S , Bollyky PL 
Published: August 2022

AbstractBacteriophage, viruses that infect bacteria, are abundant in the human body but the relationship between the phageome and bacterial population dynamics is unclear. Because bacteriophage are often highly specific to bacterial host strains and species, we asked whether bacteriophage present in cell-free DNA (cfDNA) reflect bacterial infections in sepsis. To address this, we generated a workflow for identifying and interpreting bacteriophage sequences in cfDNA and a bacteriophage characteristic dictionary. In two independent cohorts of infected patients and asymptomatic controls, we demonstrate that all individuals, septic and healthy, have a circulating phageome. Moreover, infection associates with overrepresentation of pathogen-specific phage, allowing for the study of bacterial pathogens. We further show that phage can identify pathovariantEscherichia coliinfections and distinguish between closely-related pathogenic bacterial species such asStaphylococcus aureusand frequent contaminants such as coagulase-negative Staphylococcus. Phage DNA may have utility in studying bacteriophage ecology in infection.
Evidence of hard-selective sweeps suggest independent adaptation to insecticides in Colorado potato beetle (Coleoptera:Chrysomelidae) populations
Authors: Cohen Zachary P. , Chen Yolanda H. , Groves Russell , Schoville Sean D. 
Published: August 2022

AbstractPesticide resistance provides one of the best examples of rapid evolution to environmental change. The Colorado potato beetle has a long and noteworthy history as a super-pest due to its ability to repeatedly develop resistance to novel insecticides and rapidly expand its geographic and host plant range. Here, we investigate regional differences in demography, recombination and selection using whole genome resequencing data from two highly resistant CPB populations in the United States (Hancock, Wisconsin and Long Island, New York). Demographic reconstruction corroborates historical records for a single pest origin during the colonization of the Midwestern and Eastern United States in the mid-to late-19th century and suggests that the effective population size might be higher in Long Island, NY than Hancock, WI despite contemporary potato acreage of Wisconsin being far greater. Population-based recombination maps show similar background recombination rates between these populations, as well as overlapping regions of low recombination that intersect with important metabolic detoxification genes. In both populations, we find compelling evidence for hard selective sweeps linked to insecticide resistance with multiple sweeps involving genes associated with xenobiotic metabolism, stress response, and defensive chemistry. Notably, only two candidate insecticide resistance genes are shared among both populations, but both appear to be independent hard selective sweep events. This suggests that repeated, rapid, and independent evolution of genes may underlie CPB’s pest status among geographically distinct populations.
3D RNA-scaffolded wireframe origami
Authors: Parsons Molly F. , Allan Matthew F. , Li Shanshan , Shepherd Tyson R. , Ratanalert Sakul , Zhang Kaiming , Pullen Krista M. , Chiu Wah , Rouskin Silvi , Bathe Mark 
Published: August 2022

AbstractHybrid RNA:DNA origami, in which a long RNA scaffold strand is folded into a target nanostructure via thermal annealing with complementary DNA oligos, has only been explored to a limited extent despite its unique potential for biomedical delivery of mRNA, tertiary structure characterization of long RNAs, and fabrication of artificial ribozymes. Here, we investigate design principles of wireframe RNA-scaffolded origami in three dimensions rendered as polyhedra composed of dual-duplex edges. We computationally designed, fabricated, and characterized tetrahedra folded from an EGFP-encoding messenger RNA and de Bruijn sequences, an octahedron folded with M13 transcript RNA, and an octahedron and pentagonal bipyramids folded with 23S ribosomal RNA, demonstrating the ability to make diverse polyhedral shapes with distinct structural and functional RNA scaffolds. We characterized secondary and tertiary structures using dimethyl sulfate mutational profiling and cryo-electron microscopy, revealing for the first time insight into both global and local, base-level structures of origami. Our top-down sequence design strategy enables the use of long RNAs as functional scaffolds for complex wireframe origami.
Task-dependent optimal representations for cerebellar learning
Authors: Xie Marjorie , Muscinelli Samuel , Harris Kameron Decker , Litwin-Kumar Ashok 
Published: August 2022

AbstractThe cerebellar granule cell layer has inspired numerous theoretical models of neural representations that support learned behaviors, beginning with the work of Marr and Albus. In these models, granule cells form a sparse, combinatorial encoding of diverse sensorimotor inputs. Such sparse representations are optimal for learning to discriminate random stimuli. However, recent observations of dense, low-dimensional activity across granule cells have called into question the role of sparse coding in these neurons. Here, we generalize theories of cerebellar learning to determine the optimal granule cell representation for tasks beyond random stimulus discrimination, including continuous input-output transformations as required for smooth motor control. We show that for such tasks, the optimal granule cell representation is substantially denser than predicted by classic theories. Our results provide a general theory of learning in cerebellum-like systems and suggest that optimal cerebellar representations are task-dependent.
POMC neurons modulate infant vocalizations through opioid signaling
Authors: Ortiz Gabriela M. Bosque , Dietrich Marcelo O. 
Published: August 2022

AbstractInfants cry when separated from their mothers. Here, we show that POMC neurons in the arcuate nucleus of the hypothalamus—via ß-endorphin production and signaling—modulate the crying behavior of mouse pups. The effect of POMC neurons on vocal behavior depends on the expression of µ-opioid receptors, the main receptor for ß-endorphin. Thus, POMC neurons in the hypothalamus modulate infant cry through opioid signaling.
Sequential involvements of macaque perirhinal cortex and hippocampus in semantic-like memory including spatial component
Authors: Yang Cen , Naya Yuji 
Published: August 2022

SUMMARYThe standard consolidation theory suggests the critical involvement of the hippocampus (HPC) in acquiring new knowledge, while the perirhinal cortex (PRC) is involved in its long-term storage (i.e., semantic memory). Converging studies have shown exclusive involvement of the PRC in item processing, while the HPC relates the item with a spatial context. These two lines of literature raise the following question; which brain region is involved in semantic recall that includes the spatial components? To solve this question, we applied an item-location associative (ILA) paradigm in a single-unit study using non-human primates. We trained two macaques to associate four visual item pairs with four locations on a background map before the recording sessions. In each trial, one visual item and the map image at a tilt (−90 to 90 degrees) were sequentially presented as the item-cue and the context-cue, respectively. The macaques chose the item-cue location relative to the context-cue by positioning their gaze. Neurons in both PRC and HPC but not area TE exhibited item-cue responses which signaled retrieval of item-location associative memory. This retrieval signal first appeared in the PRC before appearing in the HPC. We examined whether neural representations of the retrieved locations were related to the external space where the macaques viewed. A positive representation similarity was found in the HPC but not PRC, suggesting a contribution of the HPC to relate the retrieved location with a first-person perspective of the subjects. These results suggest their distinct but complementary contributions to semantic recall including spatial components.
PPAR-γ regulates the effector function of human TH9 cells by promoting glycolysis
Authors: Bertschi Nicole L. , Steck Oliver , Luther Fabian , Bazzini Cecilia , Meyenn Leonhard von , Felser Andrea , Keller Irene , Friedli Olivier , Freigang Stefan , Begré Nadja , Lamos Cristina , Gabutti Max Philip , Benzaquen Michael , Laimer Markus , Simon Dagmar , Nuoffer Jean-Marc , Schlapbach Christoph 
Published: August 2022

AbstractT helper 9 cells (TH9) are key drivers of allergic tissue inflammation. They are characterized by the expression of type 2 cytokines, such as IL-9 and IL-13, and the peroxisome proliferator-activated receptor gamma (PPAR-γ) transcription factor. However, the functional role of PPAR-γ in human TH9 cells remains unknown. Here, we demonstrate that PPAR-γ drives activation-induced glycolysis, which, in turn, specifically promotes the expression of IL-9, but not IL-13, in an mTORC1-dependent manner. In vitro and ex vivo experiments on skin samples of allergic contact dermatitis showed that the PPAR-γ-mTORC1-IL-9 pathway was active in TH9 cells in human skin inflammation. Additionally, we found that tissue glucose levels were dynamically regulated in acute allergic skin inflammation, suggesting that in situ glucose availability is linked to distinct immunological signals in vivo. Furthermore, paracrine IL-9 induced the lactate transporter MCT1 in IL-9R+ TH cells, where it increased aerobic glycolysis and proliferative capacity. Taken together, our findings delineate a hitherto unknown relationship between PPAR-γ-dependent glucose metabolism and the pathogenic effector function of human TH9 cells.Graphical abstract