bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatially heterogeneous microstructural development within subcortical regions from 9-13 years
Authors: Palmer C E , Pecheva D , Iversen J , Hagler DJ , Sugrue L , Nedelec P , Fan C , Thompson W K , Jernigan T L , Dale A M 
Published: June 2021

ABSTRACTDuring late childhood behavioral changes, such as increased risk-taking and emotional reactivity, have been associated with the maturation of cortico-subcortical circuits. Understanding microstructural changes in subcortical regions may aid our understanding of how individual differences in these behaviors emerge. Restriction spectrum imaging (RSI) is a framework for modelling diffusion-weighted imaging that decomposes the diffusion signal from a voxel into hindered and restricted compartments. This yields greater specificity than conventional methods of characterizing intracellular diffusion. Using RSI, we modelled voxelwise restricted isotropic, N0, and anisotropic, ND, diffusion across the brain and measured cross-sectional and longitudinal age associations in a large sample (n=8,039) from the Adolescent Brain and Cognitive Development (ABCD) study aged 9-13 years. Older participants had higher N0 and ND across subcortical regions. The largest associations for N0 were within the basal ganglia and for ND within the ventral diencephalon. Importantly, age associations varied with respect to the internal cytoarchitecture within subcortical structures, for example age associations differed across thalamic nuclei. This suggests that developmental effects may map onto specific cell populations or circuits and highlights the utility of voxelwise compared to ROI-wise analyses. Future analyses will aim to understand the relevance of this subcortical microstructural developmental for behavioral outcomes.
Interpersonal comparison of utility by measuring neural activity
Authors: Matsumori Kaosu , Iijima Kazuki , Yomogida Yukihito , Matsumoto Kenji 
Published: June 2021

AbstractAggregating well-being across individuals to reach collective decisions is one of the most fundamental problems in our society. Interpersonal comparisons of utility are pivotal and inevitable for well-being aggregation, because if utility is not interpersonally comparable, there is no rational aggregation procedure that simultaneously satisfies even mild conditions for validity (Arrow’s impossibility theorem); however, there are as yet no scientific methods for interpersonal comparison of utility. In this study, we developed a method based on brain signals. We found that the anterior cingulate and its adjacent ventromedial prefrontal activity is correlated with changes in expected utility. The ratio of lower- and higher-income participants’ neural signals coincided with estimates of their psychological pleasure by “impartial spectators.” We confirmed the validity of our interpersonal utility comparison method using an independent large-scale dataset and used the aggregated well-being from our experimental data to derive an optimal decision rule. These findings suggest that our interpersonal comparison method enables scientifically reasonable well-being aggregation by escaping Arrow’s impossibility and has implications for the fair distribution of economic goods. Our method can be used for evidence-based policy-making in nations that use cost-benefit analyses or optimal taxation theory for policy evaluation.
Patterning on the move: the effects of Hh morphogen source movement on signaling dynamics
Authors: Míguez D. G. , Iannini A. , García-Morales D. , Casares F. 
Published: June 2021

ABSTRACTMorphogens of the Hh-family trigger gene expression changes of receiving cells in a concentration-dependent manner. The outputs of the pathway include regulation of cell identity, proliferation, death or metabolism, depending on the tissue or organ. This variety of responses relies on a conserved signaling pathway. Its internal logic includes a negative feedback loop involving the Hh receptor Ptc. In this paper, we use experiments and computational models to study and compare the different spatial signaling profiles downstream of Hh in several developing Drosophila organs. We show that the spatial distribution of Ptc and the activator form of the Gli transcription factor, CiA, in wing, antenna and ocellus show similar features, but markedly different from that in the compound eye (CE). We show that these two profile types represent two time points along the signaling dynamics, and that the interplay between the spatial displacement of the Hh source in the CE and the negative feedback loop maintains the receiving cells effectively in an earlier stage of signaling. These results indicate that the dynamics of the Hh source strongly influences the signaling profile Hh elicits in receiving cells, and show how the interaction between spatial and temporal dynamics of signaling and differentiation processes can contribute to the informational versatility of the conserved Hh signaling pathway.
Human inhalable antibody fragments neutralizing SARS-CoV-2 variants for COVID-19 therapy
Authors: Minenkova Olga , Santapaola Daniela , Milazzo Ferdinando Maria , Anastasi Anna Maria , Battistuzzi Gianfranco , Chiapparino Caterina , Rosi Antonio , Gritti Giuseppe , Borleri Gianmaria , Rambaldi Alessandro , Dental Clélia , Viollet Cécile , Pagano Bruno , Salvini Laura , Marra Emanuele , Luberto Laura , Rossi Antonio , Riccio Anna , Pich Emilio Merlo , Santoro Maria Gabriella , De Santis Rita 
Published: June 2021

AbstractAs of October 2021, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global emergency, and novel therapeutics are urgently needed. Here we describe human single chain variable fragment (scFv) antibodies (76clAbs) that block an epitope of the SARS-CoV-2 spike protein essential for ACE2-mediated entry into cells. 76clAbs neutralize the delta variant and other variants being monitored (VBMs) and inhibit spike-mediated pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. In two independent animal models, intranasal administration counteracted the infection. Due to high efficiency, remarkable stability, resilience to nebulization and low production cost, 76clAbs may become a relevant tool for rapid, self-administrable early intervention in SARS-CoV-2-infected subjects independently of their immune status.
Spatio-temporal point processes as meta-models for population dynamics in heterogeneous landscapes
Authors: Zamberletti Patrizia , Papaïx Julien , Gabriel Edith , Opitz Thomas 
Published: June 2021

AbstractLandscape heterogeneity affects population dynamics, which determine species persistence, diversity and interactions. These relationships can be accurately represented by advanced spatially-explicit models (SEMs) allowing for high levels of detail and precision. However, such approaches are characterised by high computational complexity, high amount of data and memory requirements, and spatio-temporal outputs may be difficult to analyse. A possibility to deal with this complexity is to aggregate outputs over time or space, but then interesting information may be masked and lost, such as local spatio-temporal relationships or patterns. An alternative solution is given by meta-models and meta-analysis, where simplified mathematical relationships are used to structure and summarise the complex transformations from inputs to outputs. Here, we propose an original approach to analyse SEM outputs. By developing a meta-modelling approach based on spatio-temporal point processes (STPPs), we characterise spatio-temporal population dynamics and landscape heterogeneity relationships in agricultural contexts. A landscape generator and a spatially-explicit population model simulate hierarchically the pest-predator dynamics of codling moth and ground beetles in apple orchards over heterogeneous agricultural landscapes. Spatio-temporally explicit outputs are simplified to marked point patterns of key events, such as local proliferation or introduction events. Then, we construct and estimate regression equations for multi-type STPPs composed of event occurrence intensity and magnitudes. Results provide local insights into spatio-temporal dynamics of pest-predator systems. We are able to differentiate the contributions of different driver categories (i.e., spatio-temporal, spatial, population dynamics). We highlight changes in the effects on occurrence intensity and magnitude when considering drivers at global or local scale. This approach leads to novel findings in agroecology where the organisation of cultivated fields and semi-natural elements are known to play a crucial role for pest regulation. It aids to formulate guidelines for biological control strategies at global and local scale.
Targeted High-Resolution Taxonomic Identification of Bifidobacterium longum subsp. infantis Using Human Milk Oligosaccharide Metabolizing Genes
Authors: Tso Lauren , Bonham Kevin S. , Fishbein Alyssa , Rowland Sophie , Klepac-Ceraj Vanja 
Published: June 2021

AbstractBifidobacterium longum subsp. infantis (B. infantis) is one of a few microorganisms capable of metabolizing human breast milk and is a pioneer colonizer in the guts of breastfed infants. One current challenge is differentiating B. infantis from its close relatives, B. longum and B. suis. All three organisms are classified in the same species group but only B. infantis can metabolize human milk oligosaccharides (HMOs). We compared HMO-metabolizing genes across different Bifidobacterium genomes and developed B. infantis-specific primers to determine if the genes alone or the primers can be used to quickly characterize B. infantis. We showed that B. infantis is uniquely identified by the presence of five HMO-metabolizing gene clusters, tested for its prevalence in infant gut metagenomes, and validated the results using the B. infantis-specific primers. We observed that only 15 of 203 (7.4%) children under 2 years old from a cohort of US children harbored B. infantis. These results highlight the importance of developing and improving approaches to identify B. infantis. A more accurate characterization may provide insights into regional differences of B. infantis prevalence in infant gut microbiota.
Enviromic assembly increases accuracy and reduces costs of the genomic prediction for yield plasticity
Authors: Costa-Neto Germano , Crossa Jose , Fritsche-Neto Roberto 
Published: June 2021

ABSTRACTQuantitative genetics states that phenotypic variation is a consequence of genetic and environmental factors and their subsequent interaction. Here, we present an enviromic assembly approach, which includes the use of ecophysiology knowledge in shaping environmental relatedness into whole-genome predictions (GP) for plant breeding (referred to as E-GP). We propose that the quality of an environment is defined by the core of environmental typologies (envirotype) and their frequencies, which describe different zones of plant adaptation. From that, we derive markers of environmental similarity cost-effectively. Combined with the traditional genomic sources (e.g., additive and dominance effects), this approach may better represent the putative phenotypic variation across diverse growing conditions (i.e., phenotypic plasticity). Additionally, we couple a genetic algorithm scheme to design optimized multi-environment field trials (MET), combining enviromic assembly and genomic kinships to provide in-silico realizations of the future genotype-environment combinations that must be phenotyped in the field. As a proof-of-concept, we highlight E-GP applications: (1) managing the lack of phenotypic information in training accurate GP models across diverse environments and (2) guiding an early screening for yield plasticity using optimized phenotyping efforts. Our approach was tested using two non-conventional cross-validation schemes to better visualize the benefits of enviromic assembly in sparse experimental networks. Results on tropical maize show that E-GP outperforms benchmark GP in all scenarios and cases tested. We show that for training accurate GP models, the genotype-environment combinations’ representativeness is more critical than the MET size. Furthermore, we discuss theoretical backgrounds underlying how the intrinsic envirotype-phenotype covariances within the phenotypic records of (MET) can impact the accuracy of GP and limits the potentialities of predictive breeding approaches. The E-GP is an efficient approach to better use environmental databases to deliver climate-smart solutions, reduce field costs, and anticipate future scenarios.
An accurate assignment test for extremely low-coverage whole-genome sequence data
Authors: Ferrari Giada , Atmore Lane M. , Jentoft Sissel , Jakobsen Kjetill S. , Makowiecki Daniel , Barrett James H. , Star Bastiaan 
Published: June 2021

AbstractGenomic assignment tests can provide important diagnostic biological characteristics, such as population of origin or ecotype. In ancient DNA research, such characters can provide further information on population continuity, evolution, climate change, species migration, or trade, depending on archaeological context. Yet, assignment tests often rely on moderate- to high-coverage sequence data, which can be difficult to obtain for many ancient specimens and in ecological studies, which often use sequencing techniques such as ddRAD to bypass the need for costly whole-genome sequencing. We have developed a novel approach that efficiently assigns biologically relevant information (such as population identity or structural variants) in extremely low-coverage sequence data. First, we generate databases from existing reference data using a subset of diagnostic Single Nucleotide Polymorphisms (SNPs) associated with a biological characteristic. Low coverage alignment files from ancient specimens are subsequently compared to these databases to ascertain allelic state yielding a joint probability for each association. To assess the efficacy of this approach, we assigned inversion haplotypes and population identity in several species including Heliconius butterflies, Atlantic herring, and Atlantic cod. We used both modern and ancient specimens, including the first whole-genome sequence data recovered from ancient herring bones. The method accurately assigns biological characteristics, including population membership, using extremely low-coverage (e.g. 0.0001x fold) based on genome-wide SNPs. This approach will therefore increase the number of ancient samples in ecological and bioarchaeological research for which relevant biological information can be obtained.
Retinoic acid exerts sexually dimorphic effects over muscle energy metabolism and function
Authors: Zhao Yaxin , Vuckovic Marta , Yoo Hong Sik , Fox Nina , Rodriguez Adrienne , McKessy Kyler , Napoli Joseph L. 
Published: June 2021

AbstractThe retinol dehydrogenase Rdh10 catalyzes the rate-limiting reaction that converts retinol into retinoic acid (RA), an autacoid that regulates energy balance and suppresses adiposity. Relative to WT,Rdh10+/− males experienced reduced fatty-acid oxidation, glucose intolerance and insulin resistance. Running endurance decreased 40%.Rdh10+/− females increased reliance on fatty acid oxidation and did not experience glucose intolerance nor insulin resistance. Running endurance improved 2.2-fold. Estrogen increased, revealed by a 40% increase in uterine weight. Because skeletal muscle energy use restricts adiposity and insulin resistance, we assessed the mixed fiber type gastrocnemius muscle (GM) to determine the effects of endogenous RA on muscle metabolism in vivo. RA inRdh10+/− male GM decreased 38% relative to WT. TAG content increased 1.7-fold.Glut1mRNA and glucose decreased >30%.Rdh10+/− male GM had impaired electron transport chain activity, and a 60% reduction in fasting ATP. The share of oxidative fibers increased, as did expression of the myogenic transcription factorsMyogandMyf5. Centralized nuclei increased 5-fold in fibers—indicating muscle malady or repair. InRdh10+/− female GM, RA decreased only 17%, due to a 1.8-fold increase in the estrogen-induced retinol dehydrogenase, Dhrs9.Rdh10+/− female GM did not amass TAG, increase oxidative fibers, decreaseGlut1mRNA or glucose, nor increase centralized nuclei. Expression ofMyogandMyf5decreased. Electron transport chain activity increased, elevating fasting ATP >3-fold. Thus, small decreases in skeletal muscle RA affect whole body energy use, insulin resistance and adiposity, in part through estrogen-related sexual dimorphic effects on mitochondria function.
Equivalent noise characterization of human lightness constancy
Authors: Singh Vijay , Burge Johannes , Brainard David H. 
Published: June 2021

ABSTRACTA goal of visual perception is to provide stable representations of task-relevant scene properties (e.g. object reflectance) despite variation in task-irrelevant scene properties (e.g. illumination, reflectance of other nearby objects). To study such stability in the context of the perceptual representation of lightness, we introduce a threshold-based psychophysical paradigm. We measure how thresholds for discriminating the achromatic reflectance of a target object (task-relevant property) in rendered naturalistic scenes are impacted by variation in the reflectance functions of background objects (task-irrelevant property), using a two-alternative forced-choice paradigm in which the reflectance of the background objects is randomized across the two intervals of each trial. We control the amount of background reflectance variation by manipulating a statistical model of naturally-occurring surface reflectances. For low background object reflectance variation, discrimination thresholds were nearly constant, indicating that observers’ internal noise determines threshold in this regime. As background object reflectance variation increases, its effects start to dominate performance. A model based on signal detection theory allows us to express the effects of task-irrelevant variation in terms of the equivalent noise, that is relative to the intrinsic precision of the task-relevant perceptual representation. The results indicate that although naturally-occurring background object reflectance variation does intrude on the perceptual representation of target object lightness, the effect is modest - within a factor of two of the equivalent noise level set by internal noise.
Early epidemiological signatures of novel SARS-CoV-2 variants: establishment of B.1.617.2 in England
Authors: Challen Robert , Dyson Louise , Overton Christopher E. , Guzman-Rincon Laura M. , Hill Edward M. , Stage Helena B. , Brooks-Pollock Ellen , Pellis Lorenzo , Scarabel Francesca , Pascall David J. , Blomquist Paula , Tildesley Michael , Williamson Daniel , Siegert Stefan , Xiong Xiaoyu , Youngman Ben ,   Juniper, Read Jonathan M. , Gog Julia R. , Keeling Matthew J. , Danon Leon 
Published: June 2021

AbstractThe rapid emergence of SARS-CoV-2 mutants with new phenotypic properties is a critical challenge to the control of the ongoing pandemic. B.1.1.7 was monitored in the UK through routine testing and S-gene target failures (SGTF), comprising over 90% of cases by March 2021. Now, the reverse is occurring: SGTF cases are being replaced by an S-gene positive variant, which we associate with B.1.617.2. Evidence from the characteristics of S-gene positive cases demonstrates that, following importation, B.1.617.2 is transmitted locally, growing at a rate higher than B.1.1.7 and a doubling time between 5-14 days. S-gene positive cases should be prioritised for sequencing and aggressive control in any countries in which this variant is newly detected.One-Sentence SummaryThe B.1.617.2 variant of SARS-CoV-2 is replacing B.1.1.7 and emerging as the dominant variant in England, evidenced by sustained local transmission.
Prediction of severe COVID-19 cases requiring intensive care in Osaka, Japan
Authors: Kurita Junko , Sugawara Tamie , Ohkusa Yasushi 
Published: June 2021

SummaryBackgroundTo avoid exhaustion of medical resources by COVID-19 care, policy-makers must predict care needs, specifically estimating the proportion of severe cases likely to require intensive care. In Osaka prefecture, Japan, the number of these severe cases exceeded the capacity of ICU units prepared for COVID-19 from mid-April, 2021.ObjectiveThis study used a statistical model to elucidate dynamics of severe cases in Osaka and validated the model through prospective testing.MethodsThe study extended from April 3, 2020 through April 26, 2021 in Osaka prefecture, Japan prefecture. We regressed the number of severe cases on the number of severe cases the day prior and the newly onset patients of more than 21 days prior.ResultsWe selected the number of severe cases the day prior and the number of newly onset patients on 21 and 28 days prior as explanatory variables for explaining the number of severe cases based on the adjusted determinant coefficient. The adjusted coefficient of determination was greater than 0.995 and indicated good fit. Prospective out of sample three-week prediction forecast the peak date precisely, but the level was not t.Discussion and ConclusionA reason for the gap in the prospective prediction might be the emergence of variant strains.
Statistical Power or More Precise Insights into Neuro-Temporal Dynamics? Assessing the Benefits of Rapid Temporal Sampling in fMRI
Authors: Dowdle Logan T. , Ghose Geoffrey , Chen Clark C. C. , Ugurbil Kamil , Yacoub Essa , Vizioli Luca 
Published: June 2021

AbstractFunctional magnetic resonance imaging (fMRI), a non-invasive and widely used human neuroimaging method, is most known for its spatial precision. However, there is a growing interest in its temporal sensitivity. This is despite the temporal blurring of neuronal events by the blood oxygen level dependent (BOLD) signal, the peak of which lags neuronal firing by 4 to 6 seconds. Given this, the goal of this review is to answer a seemingly simple question – “What are the benefits of increased temporal sampling for fMRI?”. To answer this, we have combined fMRI data collected at multiple temporal scales, from 323 to 1000 milliseconds, with a review of both historical and contemporary temporal literature. After a brief discussion of technological developments that have rekindled interest in temporal research, we next consider the potential statistical and methodological benefits. Most importantly, we explore how fast fMRI can uncover previously unobserved neuro-temporal dynamics – effects that are entirely missed when sampling at conventional 1 to 2 second rates. With the intrinsic link between space and time in fMRI, this temporal renaissance also delivers improvements in spatial precision. Far from producing only statistical gains, the array of benefits suggest that the continued temporal work is worth the effort.