bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contextual influences of visual perceptual inferences
Authors: A-Izzeddin Emily J , Mattingley Jason B , Harrison William J 
Published: September 2022

AbstractHumans have well-documented priors for many features present in nature that guide visual perception. Despite being putatively grounded in the statistical regularities of the environment, scene priors are frequently violated due to the inherent variability of visual features from one scene to the next. However, these repeated violations do not appreciably challenge visuo-cognitive function, necessitating the broad use of priors in conjunction with context-specific information. We investigated the trade-off between participants’ internal expectations formed from both longer-term priors and those formed from immediate contextual information using a perceptual inference task and naturalistic stimuli. Notably, our task required participants to make perceptual inferences about naturalistic images using their own internal criteria, rather than making comparative judgements. Nonetheless, we show that observers’ performance is well approximated by a model that makes inferences using a prior for low-level image statistics, aggregated over many images. We further show that the dependence on this prior is rapidly re-weighted against contextual information, whether relevant or irrelevant. Our results therefore provide insight into how apparent high-level interpretations of scene appearances follow from the most basic of perceptual processes, which are grounded in the statistics of natural images.
Acute hyper- and hypoglycemia uncouples the metabolic cooperation between glucose and lactate to disrupt sleep
Authors: Carroll Caitlin M. , Stanley Molly , Raut Ryan V. , Constantino Nicholas J. , Irmen Riley E. , Mitra Anish , Snipes J. Andy , Raichle Marcus E. , Holtzman David M. , Gould Robert W. , Kishida Kenneth T. , Macauley Shannon L. 
Published: September 2022

AbstractThe sleep-wake cycle is a master regulator of metabolic and neuronal activity and when altered, can have profound effects on metabolic health and disease. Although consideration is given to how fluctuations in blood glucose affect peripheral physiology and metabolism, less is known about how glucose dysregulation impacts the intrinsic cooperation between brain metabolism and neuronal activity to regulate sleep. To understand the effect of peripheral hyper- and hypoglycemia on these relationships, we paired biosensors measuring hippocampal interstitial fluid (ISF) levels of glucose and lactate with cortical EEG/EMG recordings to produce simultaneous subsecond recordings of ISF glucose, lactate, and sleep-wake states. First, we describe a conserved temporal relationships between ISF glucose and lactate based on their intrinsic oscillations, diurnal rhythms, and sleep/wake cycles. ISF glucose and lactate oscillations are largely anti-correlated but the frequency of their oscillations dictate their power, coherence, and phase. While ISF glucose and lactate both have diurnal fluctuations, only ISF lactate is consistently elevated during wake. During wake, fluctuations in ISF lactate are associated with changes in the EEG power spectrum, suggesting wake-related activity is more closely associated with ISF lactate. Modulation of glucose availability via both hyper- or hypoglycemia disrupts the relationship between peripheral metabolism, brain metabolism, and sleep. Hyper- and hypo-glycemia increase ISF lactate, decrease NREM, and alter EEG spectral activity, again demonstrating ISF lactate drives wake-associated behaviors and disrupts sleep. Taken together, these studies demonstrate that peripheral glucose homeostasis is necessary for maintaining the relationships between brain metabolism, neuronal activity, and sleep-wake patterns and deviations in blood glucose levels are sufficient to disrupt the metabolic signature of sleep-wake states, putting the brain at risk in diseases like type-2-diabetes and Alzheimer’s disease.Graphical Abstract. Peripheral glucose homeostasis directly modifies sleep/wake patterns
Structural and functional changes of pyramidal neurons at the site of an implanted microelectrode array in rat primary motor cortex
Authors: Gregory Bronson A. , Thompson Cort H. , Salatino Joseph W. , Railing Mia J. , Zimmerman Ariana F. , Gupta Bhavna , Williams Kathleen , Beatty Joseph A. , Cox Charles L. , Purcell Erin K. 
Published: September 2022

ABSTRACTDevices capable of recording or stimulating neuronal signals have created new opportunities to understand normal physiology and treat sources of pathology in the brain. However, it is possible that the initial surgical insertion and subsequent tissue response to implanted electrodes may influence the nature of the signals detected or stimulated. In this study, we characterized structural and functional changes in pyramidal neurons surrounding silicon or polyimide-based electrodes implanted in the motor cortex of rats. Devices were captured in 300 μm-thick tissue slices collected at the 1 or 6 week time point post-implantation, and individual neurons were assessed using a combination of whole-cell electrophysiology and 2-photon imaging. We observed disruption of the dendritic arbor of neurons near (<100 μm) the device surface at both time points, as well as a significant reduction in spine densities. These effects were accompanied by a decrease in the frequency of spontaneous excitatory post-synaptic currents (sEPSCs), a loss in sag amplitude, and an increase in spike frequency adaptation at the 6 week time point. Interestingly, we also noted a significant increase in filopodial density in neurons surrounding devices. Results were similar for polyimide and silicon-based electrodes. We hypothesize that the effects observed in this study may contribute to the signal loss and instability that often accompany chronically implanted electrodes.
Improved the Protein Complex Prediction with Protein Language Models
Authors: Chen Bo , Xie Ziwei , Qiu Jiezhong , Ye Zhaofeng , Xu Jinbo , Tang Jie 
Published: September 2022

AbstractAlphaFold-Multimer has greatly improved protein complex structure prediction, but its accuracy also depends on the quality of the multiple sequence alignment (MSA) formed by the interacting homologs (i.e., interologs) of the complex under prediction. Here we propose a novel method, denoted as ESMPair, that can identify interologs of a complex by making use of protein language models (PLMs). We show that ESMPair can generate better interologs than the default MSA generation method in AlphaFold-Multimer. Our method results in better complex structure prediction than AlphaFold-Multimer by a large margin (+10.7% in terms of the Top-5 best DockQ), especially when the predicted complex structures have low confidence. We further show that by combining several MSA generation methods, we may yield even better complex structure prediction accuracy than Alphafold-Multimer (+22% in terms of the Top-5 best DockQ). We systematically analyze the impact factors of our algorithm and find out the diversity of MSA of interologs significantly affects the prediction accuracy. Moreover, we show that ESMPair performs particularly well on complexes in eucaryotes.
Parthenogenomics: insights on mutation rates and nucleotide diversity in parthenogeneticPanagrolaimusnematodes
Authors: Villegas Laura I. , Ferretti Luca , Wiehe Thomas , Waldvogel Ann-Marie , Schiffer Philipp H. 
Published: September 2022

AbstractAsexual reproduction is assumed to lead to the accumulation of deleterious mutations, and reduced heterozygosity due to the absence of recombination. Panagrolaimid nematode species display different modes of reproduction. Sexual reproduction with distinct males and females, asexual reproduction through parthenogenesis in the genusPanagrolaimus, and hermaphroditism inPropanagrolaimus. Here, we compared genomic features of free-living nematode populations in populations and species isolated from geographically distant regions to study diversity, and genome-wide differentiation under different modes of reproduction. We firstly estimated genome-wide spontaneous mutation rates in a triploid parthenogeneticPanagrolaimuspopulation, and a diploid hermaphroditicPropanagrolaimusspecies via long-term mutation-accumulation-lines. Secondly, we calculated population genetic parameters including nucleotide diversity, and fixation index (FST) between populations of asexually and sexually reproducing nematodes. Thirdly, we used phylogenetic network methods on sexually and asexually reproducingPanagrolaimuspopulations to understand evolutionary relationships between them. The estimated mutation rate was slightly lower for the asexual population, as expected for taxa with this reproductive mode. Natural polyploid asexual populations revealed higher nucleotide diversity. Despite their common ancestor, a gene network revealed a high level of genetic differentiation among asexual populations. The elevated heterozygosity found in the triploid parthenogens could be explained by the third genome copy. Given their tendentially lower mutation rates it can be hypothesized that this is part of the mechanism to evade Muller’s ratchet. Our findings in parthenogenetic triploid nematode populations seem to challenge common expectations of evolution under asexuality.
Current sequence-based models capture gene expression determinants in promoters but mostly ignore distal enhancers
Authors: Karollus Alexander , Mauermeier Thomas , Gagneur Julien 
Published: September 2022

AbstractBackgroundThe largest sequence-based models of transcription control to date have been obtained by predicting genome-wide gene regulatory assays across the human genome. This setting is fundamentally correlative, as those models are exposed during training solely to the sequence variation between human genes that arose through evolution, questioning the extent to which those models capture genuine causal signals.ResultsHere we confront predictions of state-of-the-art models of transcription regulation against data from two large-scale observational studies and five deep perturbation assays. The most advanced of these sequence-based models, Enformer, by and large captures causal determinants of human promoters. However, models fail to capture the causal effects of enhancers on expression, notably in medium to long distances and particularly for highly expressed promoters. More generally, the predicted impact of distal elements on gene expression predictions is small and the ability to correctly integrate long-range information is significantly more limited than the receptive fields of the models suggest. This is likely caused by the escalating class imbalance between actual and candidate regulatory elements as distance increases.ConclusionsOur results suggest that sequence-based models have advanced to the point that in-silico study of promoter regions and promoter variants can provide meaningful insights and we provide practical guidance on how to use them. Moreover, we foresee that it will require significantly more and particularly new kinds of data to train models accurately accounting for distal elements.
Toward Improving Immunotolerance for Stem Cell-Derived Islets
Authors: Zhou Quan , Li Hongfei , Gerace Dario , Nikolskly Igor , Wang Xi , Kenty-Ryu Jennifer , Zhang Jingping , Hinderhofer Matthew , Robinson Elaine , Melton Douglas A. 
Published: September 2022

AbstractTransplanting human stem cell-derived islets (SC-islets) is a promising therapy for insulin-dependent diabetes. While functional SC-islets have been produced for clinical application, immune rejection by the host remains a challenge. Present attempts, including chronic immunosuppression and/or physical encapsulation, have some disadvantages. Here we explore a strategy to induce an immune-tolerant environment based on the immune privilege observed in the male gonad. Sperm appears after the maturation of the immune system and development of systemic self-tolerance and the testis protects these autoreactive germ cells by the physical structure of blood-testis-barrier (BTB) and active local immunosuppression. Human SC-islets transplanted into the mouse testis can be physically protected by the BTB and we find that the testis secretes cytokines that induce a population of regulatory T cells (Tregs) that express both CD4 and CD8. We identified cytokines secreted by testis and used a cocktail of IL-2, IL-10, and TGF-β for in vitro co-culture and in vivo transplantation demonstrating improved survival of SC-islets and the induction of Tregs.One Sentence SummaryInducing local immunotolerance by suppressive cytokines for islet Transplantation.
Evaluating Working Memory Representations during the Attentional Blink: A Comparative Modeling Approach
Authors: Wang Shuyao , Karabay Aytaç , Akyürek Elkan G. 
Published: September 2022

AbstractThe nature of working memory (WM) limitations has long been debated, with several models proposed to elucidate this issue. In this study, we conducted a systematic comparison of seven visual WM models to assess their ability to account for target consolidation during the attentional blink (AB). The AB phenomenon refers to where participants often fail to encode the second of two targets when there is a short time interval of ∼500 msec or less between them, providing an opportunity to evaluate commensurate WM limitations. Despite the growing consensus on the applicability of some WM models, such as the standard mixture model and the variable precision model, to the AB domain, no study has systematically evaluated these models in this context. We addressed this gap by comparing the performance of seven widely adopted visual WM models in four different AB datasets from three separate laboratories. We fitted each model and computed the Akaike Information Criterion (AIC) values at an individual level across different conditions and experiments, based on which we compared the models. We found that most models, excluding the variable precision model, fit well to AB datasets. We nevertheless also observed that experimental properties, such as the choice of stimuli or the spatial arrangement of targets resulted in different model rankings. This systematic evaluation of WM models in the AB context can help AB researchers select the most appropriate models, and thereby enhance the understanding of WM consolidation under time constraints and the mechanisms behind the AB phenomenon.
Functional connectivity across the human subcortical auditory system using an autoregressive matrix-Gaussian copula graphical model approach with partial correlations
Authors: Chandra Noirrit Kiran , Sitek Kevin R. , Chandrasekaran Bharath , Sarkar Abhra 
Published: September 2022

Abstract/SummaryThe auditory system comprises multiple subcortical brain structures that process and refine incoming acoustic signals along the primary auditory pathway. Due to technical limitations of imaging small structures deep inside the brain, most of our knowledge of the subcortical auditory system is based on research in animal models using invasive methodologies. Advances in ultra-high field functional magnetic resonance imaging (fMRI) acquisition have enabled novel non-invasive investigations of the human auditory subcortex, including fundamental features of auditory representation such as tonotopy and periodotopy. However, functional connectivity across subcortical networks is still underexplored in humans, with ongoing development of related methods. Traditionally, functional connectivity is estimated from fMRI data with full correlation matrices. However, partial correlations reveal the relationship between two regions after removing the effects of all other regions, reflecting more direct connectivity. Partial correlation analysis is particularly promising in the ascending auditory system, where sensory information is passed in an obligatory manner, from nucleus to nucleus up the primary auditory pathway, providing redundant but also increasingly abstract representations of auditory stimuli. While most existing methods for learning conditional dependency structures based on partial correlations assume independently and identically Gaussian distributed data, fMRI data exhibit significant deviations from Gaussianity as well as high temporal autocorrelation. In this paper, we developed an autoregressive matrix-Gaussian copula graphical model (ARMGCGM) approach to estimate the partial correlations and thereby infer the functional connectivity patterns within the auditory system while appropriately accounting for autocorrelations between successive fMRI scans. Our results show strong positive partial correlations between successive structures in the primary auditory pathway on each side (left and right), including between auditory midbrain and thalamus, and between primary and associative auditory cortex. These results are highly stable when splitting the data in halves according to the acquisition schemes and computing partial correlations separately for each half of the data, as well as across cross-validation folds. In contrast, full correlation-based analysis identified a rich network of interconnectivity that was not specific to adjacent nodes along the pathway. Overall, our results demonstrate that unique functional connectivity patterns along the auditory pathway are recoverable using novel connectivity approaches and that our connectivity methods are reliable across multiple acquisitions.
Bet hedging is not sufficient to explain germination patterns of a winter annual plant
Authors: Siegmund Gregor-Fausto , Moeller David A. , Eckhart Vincent M. , Geber Monica A. 
Published: September 2022

AbstractBet hedging consists of life history strategies that buffer against environmental variability by trading off immediate and long-term fitness. Delayed germination in annual plants is a classic example of bet hedging, and is often invoked to explain low germination fractions. We examined whether bet hedging explains low and variable germination fractions among 20 populations of the winter annual plantClarkia xantianassp.xantianathat experience substantial variation in reproductive success among years. Leveraging 15 years of demographic monitoring and 3 years of field germination experiments, we assessed the fitness consequences of seed banks and compared optimal germination fractions from a density-independent bet-hedging model to observed germination fractions. We did not find consistent evidence of bet hedging or the expected trade-off between arithmetic and geometric mean fitness, though delayed germination increased long-term fitness in 7 of 20 populations. Optimal germination fractions were 2 to 5 times higher than observed germination fractions, and among-population variation in germination fractions was not correlated with risks across the life cycle. Our comprehensive test suggests that bet hedging is insufficient to explain the observed germination patterns. Understanding variation in germination strategies will likely require integrating bet hedging with complementary forces shaping the evolution of delayed germination.
Topographically driven microclimatic gradients shape patterns of forest structure, diversity, and composition at a forest-grassland transition zone
Authors: McNichol Bailey H. , Wang Ran , Hefner Amanda , Helzer Chris , McMahon Sean M. , Russo Sabrina E. 
Published: September 2022

AbstractGlobally, forests provide important ecosystem services, but anthropogenic change may shift the boundaries of forested biomes, because small-scale environmental changes govern biome transitions. This is especially true in semi-arid forests, where minor topographic and microclimatic changes influence forest functioning and transitions to open biomes such as grasslands. However, we lack quantitative descriptions of topographically driven microclimate variation and how it shapes forest structure, diversity, and composition in these transition zones.Leveraging a 20.2-ha forest inventory plot (Niobrara plot) at a semi-arid forest-grassland transition zone in the Niobrara River valley (Nebraska, USA), we paired data on abundances and distributions of seedlings, saplings, and adults of woody species with topographic and microclimate data to test the hypothesis that if topographic variation causes variation in microclimate that affects forest function, then forest structure, diversity, and composition should vary significantly with topography and microclimate.Microclimatic variation within the Niobrara plot strongly corresponded with topography, creating a sharp water availability and exposure gradient from the river floodplain to the forest-grassland transition zone. The magnitude of microclimate variation corresponded to that of regional macroclimate variation. Mean soil moisture was 10.2% lower along the higher-elevation transition zone than in the canyon bottoms, corresponding to variation across approximately 2.5 degrees of longitude. Mean air temperature increased by 2.2 °C from the canyon bottoms to upper canyon, corresponding to variation across approximately 3 degrees of latitude.Forest structure, diversity, and composition correlated strongly with topographic and microclimatic gradients. More complex forest structure and higher species richness of adults and saplings occurred in moister, less exposed habitats with steeper slopes and lower elevations, whereas seedling stem density and richness were higher in higher-light, moister habitats at lower elevations. Species occupied well-defined topographic niches, promoting high beta diversity along topographic and microclimatic gradients and high species turnover from the floodplain to the transition zone.Synthesis: Microclimatic and topographic variation drive patterns of structure, diversity, and composition in the forests at this forest-grassland transition zone. As the macroclimate becomes warmer and drier, topographically mediated microclimatic refuges supporting diverse, structurally complex forested ecosystems may shrink in semi-arid regions.
Leishmania major centrinknock-out parasites alter the kynurenine- aryl hydrocarbon receptor signaling to produce a pro-inflammatory response
Authors: Oljuskin Timur , Azodi Nazli , Volpedo Greta , Bhattacharya Parna , Ismail Nevien , Hamano Shinjiro , Matlashewski Greg , Satoskar Abhay R. , Gannavaram Sreenivas , Nakhasi Hira L. 
Published: September 2022

SummaryLeishmaniasis is a parasitic disease that is prevalent in approximately 88 countries, and yet no licensed human vaccine exists against it. Towards control of leishmaniasis, we have developedLeishmania major centringene deletion mutant strains (LmCen-/-) as a live attenuated vaccine, which induces a strong Th1 response to provide IFN-γ-mediated protection to the host. However, the immune mechanisms of such protection remain to be understood. Metabolomic reprogramming of the host cells followingLeishmania-infection has been shown to play a critical role in pathogenicity and shaping the immune response following infection. Here, we applied untargeted mass spectrometric analysis to study the metabolic changes induced by infection withLmCen-/-and compared those with virulentL. majorparasite infection to identify the immune mechanism of protection. Our data shows that immunization withLmCen-/-parasites, in contrast to virulentL. majorinfection, alters tryptophan metabolism to down-regulate kynurenine-AhR signaling and promote a pro-inflammatory response.