bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colonic Oxygen Microbubbles Augment Systemic Oxygenation and CO2 Removal in a Porcine Smoke Inhalation Model of Severe Hypoxia
Authors: Mountford Paul. A. , Leiphrakpam Premila. D. , Weber Hannah. R. , McCain Andrea , Scribner Robert. M. , Scribner Robert. T. , Duarte Ernesto M. , Chen Jie , Borden Mark. A. , Buesing Keely. L. 
Published: December 2021

AbstractInhalation injury can lead to pulmonary complications resulting in the development of respiratory distress and severe hypoxia. Respiratory distress is one of the major causes of death in critically ill patients with a reported mortality rate of up to 45%. The present study focuses on the effect of oxygen microbubble (OMB) infusion via the colon in a porcine model of smoke inhalation-induced lung injury. Juvenile female Duroc pigs (n=6 colonic OMB, n=6 no treatment) ranging from 39-51 kg in weight were exposed to smoke under general anesthesia for 2 h. Animals developed severe hypoxia 48 h after smoke inhalation as reflected by reduction in SpO2 to 66.3 % ± 13.1% and PaO2 to 45.3 ± 7.6 mmHg, as well as bilateral diffuse infiltrates demonstrated on chest x-ray. Colonic OMB infusion (75 – 100 mL/kg dose) resulted in significant improvements in systemic oxygenation as demonstrated by an increase in PaO2 of 13.2 ± 4.7 mmHg and SpO2 of 15.2% ± 10.0% out to 2.5 h, compared to no-treatment control animals that experienced a decline in PaO2 of 8.2 ± 7.9 mmHg and SpO2 of 12.9% ± 18.7% over the same timeframe. Likewise, colonic OMB decreased PaCO2 and PmvCO2 by 19.7 ± 7.6 mmHg and 7.6 ± 6.7 mmHg, respectively, compared to controls that experienced increases in PaCO2 and PmvCO2 of 17.9 ± 11.7 mmHg and 18.3 ± 11.2 mmHg. We conclude that colonic OMB therapy has potential to treat patients experiencing severe hypoxemic respiratory failure.One Sentence SummaryEnteral oxygen microbubbles increase systemic oxygen and decrease carbon dioxide levels in acutely hypoxic pigs after smoke inhalation-induced respiratory failure.
Volatile-mediated signaling induces resistance of barley against infection with the biotrophic fungusBlumeria graminisf.sp.hordei
Authors: Laupheimer Silvana , Proels Reinhard , Unsicker Sybille B. , Hückelhoven Ralph 
Published: December 2021

AbstractPlants have evolved a vast variety of secondary metabolites to counteract biotic stress. Volatile organic compounds (VOCs) are carbon-based molecules induced by herbivore attack or pathogen infection. A mixture of plant VOCs is released for direct or indirect plant defense, plant-plant or plant-insect communication. Recent studies suggest that VOCs can also induce biotic stress resistance in distant organs and neighboring plants. Among other VOCs, green leaf volatiles (GLVs) are quickly released by plant tissue after the onset of herbivory or wounding.We analysed VOCs emitted by 13-day old barley plants (Hordeum vulgareL.) after mechanical wounding using passive absorbers and TD-GC/MS detection. We investigated the influence of pure (Z)-3-hexenyl acetate (Z3HAC) as well as complex VOCs from wounded barley plants on the barley - powdery mildew interaction by pre-exposure in a static and a dynamic headspace connected to a powdery mildew susceptibility assay.GLVs dominated the volatile profile of wounded barley plants with Z3HAC as the most prominent compound. Pre-exposure with Z3HAC resulted in induced resistance of barley against fungal infection. Barley complex volatiles emitted after mechanical wounding, similarly, enhanced resistance in receiver plants.We found volatile-induced modification of the interaction towards an enhanced resistance against fungal infection. In addition, Z3HAC triggered a modulation of the alcohol dehydrogenase isoenzyme activity in receiver plants, a physiological response that possibly contributes to induced resistance. Plant-originated volatile metabolites could be a useful supplementation for future agronomic or horticultural practices.HighlightVolatile-induced modification of the barley-powdery mildew interaction towards an enhanced resistance against fungal infection.
Altered Task Demands Lead to a Division of Labor for Sensory and Cognitive Processing in the Middle Temporal Area
Authors: Scott Hayden , Wimmer Klaus , Pasternak Tatiana , Snyder Adam C. 
Published: December 2021

AbstractNeurons in the primate Middle Temporal (MT) area signal information about visual motion and work together with the lateral prefrontal cortex (LPFC) to support memory-guided comparisons of visual motion direction. These areas are reciprocally connected, and both contain neurons that signal visual motion direction in the strength of their responses. Previously, LPFC was shown to display marked changes in stimulus coding with altered task demands, including changes in selectivity for motion direction, trial-to-trial variability in responses, and comparison effects. Since MT and LPFC are directly interconnected, we sought to determine if MT neurons display similar dependence on task demands. We found that active participation in a motion direction comparison task affected both sensory and non-sensory activity in MT neurons. In fact, neurons that became less-selective for motion direction during the active task showed increased signalling for cognitive aspects of the task. This heterogeneity in neural modification with heightened task demands suggests a division of labor in MT, whereby sensory and cognitive signals are both heightened in different subpopulations of neurons.
The arousal-motor hypothesis of dopamine function: evidence that dopamine facilitates reward seeking in part by maintaining arousal
Authors: Kaźmierczak Marcin , Nicola Saleem M. 
Published: December 2021

AbstractDopamine facilitates approach to reward via its actions on dopamine receptors in the nucleus accumbens. For example, blocking either D1 or D2 dopamine receptors in the accumbens reduces the proportion of reward-predictive cues to which rats respond with cued approach. Recent evidence indicates that accumbens dopamine also promotes wakefulness and arousal, but the relationship between dopamine’s roles in arousal and reward seeking remains unexplored. Here, we show that the ability of systemic or intra-accumbens injections of the D1 antagonist SCH23390 to reduce cued approach to reward depends on the animal’s state of arousal. Handling the animal, a manipulation known to increase arousal, was sufficient to reverse the behavioral effects of the antagonist. In addition, SCH23390 reduced spontaneous locomotion and increased time spent in sleep postures, both consistent with reduced arousal, but also increased time spent immobile in postures inconsistent with sleep. In contrast, the ability of the D2 antagonist haloperidol to reduce cued approach was not reversible by handling. Haloperidol reduced spontaneous locomotion but did not increase sleep postures, instead increasing immobility in non-sleep postures. We place these results in the context of the extensive literature on dopamine’s contributions to behavior, and propose the arousal-motor hypothesis. This novel synthesis, which proposes that two main functions of dopamine are to promote arousal and facilitate motor behavior, accounts both for our findings and many previous behavioral observations that have led to disparate and conflicting conclusions.
Directional Tuning of Phase Precession Properties in the Hippocampus
Authors: Yiu Yuk-Hoi , Leutgeb Jill K. , Leibold Christian 
Published: December 2021

AbstractRunning direction in the hippocampus is encoded by rate modulations of place field activity but also by spike timing correlations known as theta sequences. Whether directional rate codes and the directionality of place field correlations are related, however, has so far not been explored and therefore the nature of how directional information is encoded in the cornu ammonis remains unresolved. Here, using a previously published dataset that contains the spike activity of rat hippocampal place cells in the CA1, CA2 and CA3 subregions during free foraging of male Long-Evans rats in a 2D environment, we found that rate and spike timing codes are related. Opposite to a place field’s preferred firing rate direction spikes are more likely to undergo theta phase precession and, hence, more strongly impact paired correlations. Furthermore, we identified a subset of field pairs whose theta correlations are intrinsic in that they maintain the same firing order when the running direction is reversed. Both effects are associated with differences in theta phase distributions, and are more prominent in CA3 than CA1. We thus hypothesize that intrinsic spiking is most prominent when the directionally modulated sensory-motor drive of hippocampal firing rates is minimal, suggesting that extrinsic and intrinsic sequences contribute to phase precession as two distinct mechanisms.
Increased context adjustment is associated with auditory sensitivities but not with autistic traits
Authors: Randeniya R. , Mattingley J. B. , Garrido M. I. 
Published: December 2021

AbstractBayesian models of autism suggest that disruptions in context-sensitive prediction error weighting may underpin sensory perceptual alterations, such as hypersensitivities. We used an auditory oddball paradigm with pure tones arising from high or low uncertainity contexts to determine whether autistic individuals display differences in context adjustment relative to neurotypicals. We did not find group differences in early prediction error responses indexed by mismatch negativity. However, the autism group had larger evoked responses to outliers, at 300ms latency suggesting a greater reorienting of attention to surprising sounds. A dimensional approach revealed a positive correlation between context-dependent prediction errors and auditory sensitivities, but not with autistic traits. These findings suggest that autism studies may benefit from accounting for sensory sensitivities in group comparisons.Lay SummaryWe find no differences in brain responses (EEG amplitudes) between autistic and neurotypical adults when listening to two contexts of tone patterns. However, we find a larger difference in the EEG amplitude when shifting between low to high uncertainity streams of tones, as sensory sensitivities (but not autistic traits) increase. These findings show that perceptual alterations maybe a function of sensory sensitivities, but not necessarily autistic traits. We suggest that future EEG studies in autism may benefit from accounting for sensory sensitivities.
Age- and sex-related differences in baboon (Papio anubis) gray matter covariation
Authors: Mulholland M. M. , Meguerditchian A. , Hopkins W. D. 
Published: December 2021

AbstractAge-related changes in cognition, brain morphology, and behavior are exhibited in several primate species. Baboons, like humans, naturally develop Alzheimer’s disease-like pathology and cognitive declines with age and are an underutilized model for studies of aging. To determine age-related differences in gray matter covariation of 89 olive baboons (Papio anubis), we used source-based morphometry (SBM) to analyze data from magnetic resonance images. We hypothesized that we would find significant age effects in one or more SBM components, particularly those which include regions influenced by age in humans and other nonhuman primates (NHPs). A multivariate analysis of variance revealed that individual weighted gray matter covariation scores differed across the age classes. Elderly baboons contributed significantly less to gray matter covariation components including the brainstem, superior parietal cortex, thalamus, and pallidum compared to juveniles, and middle and superior frontal cortex compared to juveniles and young adults (p<0.05). Future studies should examine the relationship between the changes in gray matter covariation reported here and age-related cognitive decline.
Geographic variation in larval cold tolerance and exposure across the invasion front of a widely established forest insect
Authors: Hafker Petra , Thompson Lily M. , Walter Jonathan A. , Parry Dylan , Grayson Kristine L. 
Published: December 2021

AbstractAs the global climate changes, high and low temperature extremes can drive changes in species distributions. Across the range of a species, thermal tolerance can experience plasticity and may undergo selection, shaping resilience to temperature stress. In this study, we measured variation in the lower thermal tolerance of early instar larvae of an invasive forest insect, Lymantria dispar dispar L. (Lepidoptera: Erebidae), using populations sourced from the climatically diverse invasion of the Eastern United States. In two chill coma recovery experiments, we recorded recovery time following a period of exposure to a non-lethal cold temperature. A third experiment quantified growth responses after chill coma recovery to evaluate sublethal effects. Our results indicate that cold tolerance is linked to regional climate, with individuals from cold climate populations recovering faster from chill coma. While this geographic gradient is seen in many species, detecting this pattern is notable for an introduced species founded from a single point-source introduction. We demonstrate that the cold temperatures used in our experiments occur in nature from cold snaps after spring hatching, but negative impacts to growth and survival appear low. We expect that population differences in cold temperature performance manifest more from differences in temperature-dependent growth than acute exposure. Evaluating intraspecific variation in cold tolerance increases our understanding of the role of climatic gradients on the physiology of an invasive species, and contributes to tools for predicting further expansion.Summary StatementChill coma recovery experiments demonstrate geographic variation in cold temperature tolerance for a widespread invasive species, and the risk of early season exposure differs across the invasion front.
Trapping of Nicotinic Acetylcholine Receptor Ligands Assayed by in vitro Cellular Studies and in vivo PET Imaging
Authors: Zhang Hannah J. , Zammit Matthew , Kao Chien-Min , Govind Anitha P , Mitchell Samuel , Holderman Nathanial , Bhuiyan Mohammed , Freifelder Richard , Zhuang Xiaoxi , Mukherjee Jogeshwar , Chen Chin-Tu , Green William N. 
Published: December 2021

AbstractA question relevant to nicotine addiction is how nicotine and other nicotinic receptor membranepermeant ligands, such as the anti-smoking drug varenicline (Chantix), distribute in brain. Ligands, like varenicline, with high pKa and high-affinity for α4β2-type nicotinic receptors (α4β2Rs) are trapped in intracellular acidic vesicles containing α4β2Rs in vitro. Nicotine, with lower pKa and α4β2R affinity, is not trapped. Here, we extend our results by imaging nicotinic PET ligands in vivo in mouse brain and identifying the trapping brain organelle in vitro as Golgi satellites (GSats). Two PET 18F-labelled imaging ligands were chosen: [18F]2-FA85380 (2-FA) with varenicline-like pKa and affinity and [18F]Nifene with nicotine-like pKa and affinity. [18F]2-FA PET-imaging kinetics were very slow consistent with 2-FA trapping in α4β2R-containing GSats. In contrast, [18F]Nifene kinetics were rapid, consistent with its binding to α4β2Rs but no trapping. Specific [18F]2-FA and [18F]Nifene signals were eliminated in β2 subunit knockout mice or by acute nicotine injections demonstrating binding to sites on β2-containing receptors. Chloroquine, which dissipates GSat pH gradients, reduced [18F]2-FA distributions while having little effect on [18F]Nifene distributions in vivo consistent with only [18F]2-FA trapping in GSats. These results are further supported by in vitro findings where dissipation of GSat pH gradients blocks 2-FA trapping in GSats without affecting Nifene. By combining in vitro and in vivo imaging, we mapped both the brain-wide and subcellular distributions of weak-base nicotinic receptor ligands. We conclude that ligands, such as varenicline, are trapped in neurons in α4β2R-containing GSats, which results in very slow release long after nicotine is gone after smoking.SignificanceMechanisms of nicotine addiction remain poorly understood. An earlier study using in vitro methods found that the anti-smoking nicotinic ligand, varenicline (Chantix) was trapped in α4β2R-containing acidic vesicles. Using a fluorescent labeled high-affinity nicotinic ligand, this study provided evidence that these intracellular acidic vesicles were α4β2R-containing Golgi satellites. In vivo PET imaging with F-18 labeled nicotinic ligands provided additional evidence that differences in PET ligand trapping in acidic vesicles were the cause of differences in PET ligand kinetics and subcellular distributions. These findings combining in vitro and in vivo imaging revealed new mechanistic insights into the kinetics of weak base PET imaging ligands and the subcellular mechanisms underlying nicotine addiction.
DISA tool: discriminative and informative subspace assessment with categorical and numerical outcomes
Authors: Alexandre Leonardo , Costa Rafael S. , Henriques Rui 
Published: December 2021

AbstractMotivationPattern discovery and subspace clustering play a central role in the biological domain, supporting for instance putative regulatory module discovery from omic data for both descriptive and predictive ends. In the presence of target variables (e.g. phenotypes), regulatory patterns should further satisfy delineate discriminative power properties, well-established in the presence of categorical outcomes, yet largely disregarded for numerical outcomes, such as risk profiles and quantitative phenotypes.ResultsDISA (Discriminative and Informative Subspace Assessment), a Python software package, is proposed to assess patterns in the presence of numerical outcomes using well-established measures together with a novel principle able to statistically assess the correlation gain of the subspace against the overall space. Results confirm the possibility to soundly extend discriminative criteria towards numerical outcomes without the drawbacks well-associated with discretization procedures. A case study is provided to show the properties of the proposed method.AvailabilityDISA is freely available at https://github.com/JupitersMight/DISA under the MIT license.Contact{leonardoalexandre@tecnico.ulisboa.pt,rmch@tecnico.ulisboa.pt} and {rs.costa@fct.unl.pt}
A direct high-throughput protein quantification strategy facilitates discovery and characterization of a celastrol-derived BRD4 degrader
Authors: Payne N. Connor , Maksoud Semer , Tannous Bakhos A. , Mazitschek Ralph 
Published: December 2021

ABSTRACTWe describe a generalizable time-resolved Förster resonance energy transfer (TR-FRET)-based platform to profile the cellular action of heterobifunctional degraders (or proteolysis-targeting chimeras; PROTACs), capable of both accurately quantifying protein levels in whole cell lysates in less than 1 h and measuring small-molecule target engagement to en-dogenous proteins, here specifically for human bromodomain-containing protein 4 (BRD4). The detection mix consists of a single primary antibody targeting the protein of interest, a luminescent donor-labeled anti-species nanobody, and a fluorescent acceptor ligand. Importantly, our strategy can readily be applied to other targets of interest and will greatly facilitate the cell-based profiling of small molecule inhibitors and PROTACs in high-throughput format with unmodified cell lines. We further-more validate our platform in the characterization of celastrol, ap-quinone methide-containing pentacyclic triterpenoid, as a broad cysteine-targeting E3 ubiquitin ligase warhead for potent and efficient targeted protein degradation.
Nanotrap Particles Improve Nanopore Sequencing of SARS-CoV-2 and Other Respiratory Viruses
Authors: Andersen P , Barksdale S , Barclay RA , Smith N , Fernandes J , Besse K , Goldfarb D , Barbero R , Dunlap R , Jones-Roe T , Kelly R , Miao S , Ruhunusiri C , Munns A , Mosavi S , Sanson L , Munns D , Sahoo S , Swahn O , Hull K , White D , Kolb K , Noroozi F , Seelam J , Patnaik A , Lepene B 
Published: December 2021

AbstractPresented here is a magnetic hydrogel particle enabled workflow for capturing and concentrating SARS-CoV-2 from diagnostic remnant swab samples that significantly improves sequencing results using the Oxford Nanopore Technologies MinION sequencing platform. Our approach utilizes a novel affinity-based magnetic hydrogel particle, circumventing low input sample volumes and allowing for both rapid manual and automated high throughput workflows that are compatible with nanopore sequencing. This approach enhances standard RNA extraction protocols, providing up to 40x improvements in viral mapped reads, and improves sequencing coverage by 20-80% from lower titer diagnostic remnant samples. Furthermore, we demonstrate that this approach works for contrived influenza virus and respiratory syncytial virus samples, suggesting that it can be used to identify and improve sequencing results of multiple viruses in VTM samples. These methods can be performed manually or on a KingFisher Apex system.
Temporal response characterization across individual multiomics profiles of prediabetic and diabetic subjects
Authors: Zheng Minzhang , Piermarocchi Carlo , Mias George I. 
Published: December 2021

AbstractLongitudinal deep multi-omics profiling, which combines biomolecular, physiological, environmental and clinical measures data, shows great promise for precision health. However, integrating and understanding the complexity of such data remains a big challenge. Here we propose a bottom-up framework starting from assessing single individuals’ multi-omics time series, and using individual responses to assess multi-individual grouping based directly on similarity of their longitudinal deep multi-omics profiles. We applied our method to individual profiles from a study profiling longitudinal responses in type 2 diabetes mellitus. After generating periodograms for individual subject omics signals, we constructed within-person omics networks and analyzed personal-level immune changes. The results showed that our method identified both individual-level responses to immune perturbation, and the clusters of individuals that have similar behaviors in immune response and which was associated to measures of their diabetic status.
Ongoing transposition in cell culture reveals the phylogeny of diverse Drosophila S2 sub-lines
Authors: Han Shunhua , Dias Guilherme , Basting Preston J. , Nelson Michael G. , Patel Sanjai , Marzo Mar , Bergman Casey M. 
Published: December 2021

ABSTRACTCultured cells are widely used in molecular biology despite poor understanding of how cell line genomes change in vitro over time. Previous work has shown that Drosophila cultured cells have a higher transposable element (TE) content than whole flies, but whether this increase in TE content resulted from an initial burst of transposition during cell line establishment or ongoing transposition in cell culture remains unclear. Here we sequence the genomes of 25 sub-lines of Drosophila S2 cells and show that TE insertions provide abundant markers for the phylogenetic reconstruction of diverse sub-lines in a model animal cell culture system. Analysis of DNA copy number evolution across S2 sub-lines revealed dramatically different patterns of genome organization that support the overall evolutionary history reconstructed using TE insertions. Analysis of TE insertion site occupancy and ancestral states support a model of ongoing transposition dominated by episodic activity of a small number of retrotransposon families. Our work demonstrates that substantial genome evolution occurs during long-term Drosophila cell culture, which may impact the reproducibility of experiments that do not control for sub-line identity.