bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reward actively engages both implicit and explicit components in dual force field adaptation
Authors: Forano Marion , Franklin David W. 
Published: August 2023

ABSTRACTMotor learning occurs through multiple mechanisms, including unsupervised, supervised (error-based) and reinforcement (reward-based) learning. Although studies have shown that reward leads to an overall better motor adaptation, the specific processes by which reward influences adaptation are still unclear. Here, we examine how the presence of reward affects dual-adaptation to novel dynamics, and distinguish its influence on implicit and explicit learning. Participants adapted to two opposing force fields in an adaptation/de-adaptation/error-clamp paradigm, where five levels of reward (a score and a digital face) were provided as participants reduced their lateral error. Both reward and control (no reward provided) groups simultaneously adapted to both opposing force fields, exhibiting a similar final level of adaptation, which was primarily implicit. Triple-rate models fit to the adaptation process found higher learning rates in the fast and slow processes, and a slightly increased fast retention rate for the reward group. While differences in the slow learning rate were only driven by implicit learning, the large difference in the fast learning rate was mainly explicit. Overall, we confirm previous work showing that reward increases learning rates, extending this to dual-adaptation experiments, and demonstrating that reward influences both implicit and explicit adaptation. Specifically, we show that reward acts primarily explicitly on the fast learning rate and implicitly on the slow learning rates.New and NoteworthyHere we show that rewarding participants’ performance during dual force field adaptation primarily affects the initial rate of learning and the early timescales of adaptation, with little effect on the final adaptation level. However, reward affects both explicit and implicit components of adaptation. While the learning rate of the slow process is increased implicitly, the fast learning and retention rates are increased through both implicit components and the use of explicit strategies.
Spatial coding of conspecifics in subpopulations of hindbrain pyramidal cells of the gymnotiform electrosensory system
Authors: Milam Oak E , Marsat Gary 
Published: August 2023

AbstractLocalizing the source of a signal requires sophisticated neural mechanisms and we are still uncovering the coding principles that support accurate spatial processing. Weakly electric fish can detect and localize distant conspecifics, but the way this spatial information is encoded is unclear. Here, we investigate the spatial representation of conspecific signals in the hindbrain to determine how the properties of the heterogenous population of pyramidal cells affect the spatial coding accuracy of conspecific signals. We hypothesize that specific subsets of cells provide more accurate spatial information about conspecific location. We stimulated the fish with an artificial signal that replicates both the spatial and temporal structure of conspecific signals. We recorded from cells with various receptive field positions covering the entire body surface and analyzed the spike train with spike-train distance metrics to determine how accurately the location of the stimulus is encoded. We found that some pyramidal cells (such as ON-type, and those within the deep layer) encode the spatial information more accurately while other subgroups (OFF-type, and superficial layer) provide less accurate information. Our results help us understand how the heterogeneity of a population of cells allow the efficient processing of signals and suggest that a segregation of the spatial information stream starts earlier in the sensory pathway.
High-frequency cortical neural inputs to muscles during movement cancellation
Authors: Zicher B , Avrillon S , Ibáñez J , Farina D 
Published: August 2023

AbstractCortical beta (13-30 Hz) and gamma (30-60 Hz) oscillations have been investigated during motor processing. Although they are at frequencies greater than the dynamic bandwidth of muscle contraction, these oscillations are partly transmitted from the cortex to motoneurons and muscles. Little is known about when and why this transmission occurs. We developed an experimental approach to examine these high frequency inputs to motoneurons under different motor states while maintaining a stable force, thus constraining behaviour. We acquired brain and muscle activity during a ‘GO’/’NO-GO’ task. In this experiment, the effector muscle for the task (tibialis anterior) was kept tonically active during the trials, while participants (N=9) reacted to sequences of auditory stimuli by either keeping the contraction unaltered (‘NO-GO’ trials), or by quickly performing a ballistic contraction (‘GO’ trials). Motor unit (MU) firing activity was extracted from high-density surface and intramuscular electromyographic signals, and the changes in its spectral contents in the ‘NO-GO’ trials were analysed. We observed an increase in beta and low-gamma (30-45 Hz) activity post ‘NO-GO’ cue at the brain and muscle levels. There was also an increase in the activity within 8-12 Hz, which was only observed at the muscle level. Overall, our results suggest that the cortical processing of movement cancellation occurs at least in part via increased power of high-frequency oscillations transmitted downstream to the muscles. These changes occur without alterations in behaviour, suggesting that the downstream transmission of these high-frequency oscillations does not have a direct functional impact.
Unveiling the benefits and gaps of wild pollinators on nutrition and income
Authors: Duarte Gabriela T. , Schuster Richard , Mitchell Matthew G.E. 
Published: August 2023

AbstractInsect pollinators play a crucial role in global crop production, enhancing fruit and seed yield, improving fruit quality, and increasing crop nutritional value. However, wild pollinator populations worldwide have been experiencing alarming declines. This study investigates the contribution of wild pollinators to nutrition and farmers’ income in Canada, while examining the spatial distribution of these services. Using publicly available data on crop types, yields, nutrient content, and farm gate values, alongside information on natural habitats, we estimated the benefits of wild pollinators across national agricultural landscapes. Our findings reveal that these pollinators sustain approximately 24.4 million equivalent people each year in terms of nutrition and generate an annual income of nearly CAD$2.8 billion for farmers. However, significant benefit gaps exist due to the lack of nearby pollinator habitats and insufficient pollination of dependent crops on a national scale. Addressing these gaps could provide an additional nutrition supply for nearly 30 million equivalent people and increase farmer income by CAD$3 billion. We discuss how and where efforts focused on preserving and enhancing wild pollinator habitats, promoting sustainable farming practices, and raising awareness among stakeholders are crucial for the long-term viability of wild pollinator populations and the sustainability of agricultural systems. This research underscores the urgent need for a national strategy aimed at safeguarding wild pollinators. Implementing such a strategy would not only contribute to strengthening local economies in the regions highlighted in our work but also ensure the production of nutritionally essential food.
A Fit for Purpose Approach to Evaluate Detection of Amino Acid Substitutions in Shotgun Proteomics
Authors: Lundgren Taylor J. , Clark Patricia L. , Champion Matthew M. 
Published: August 2023

AbstractAmino acid substitutions (AAS) change a protein from its genome-expected sequence. Accumulation of substitutions in proteins underlie numerous diseases and antibiotic mechanisms. Accurate global detection of substitutions and their frequencies would help characterize these mechanisms. Measurement of AAS using shotgun proteomics is attractive due to its high sensitivity and untargeted acquisition. However, identifying substituted peptide-spectra requires search strategies that extrapolate beyond the genome, which can introduce bias. To characterize this bias, we constructed a “ground-truth” approach using the similarities between theEscherichia coliandSalmonella typhimuriumproteomes to effectively model the complexity of distinguishing substitutions from genomic peptides. Shotgun proteomics on combined whole cell lysates from both organisms generated a library representing nearly 100,000 peptide-spectra and 4,161 distinct peptide sequences corresponding to genome-level single AAS with defined stoichiometry. We tested the ability to identifyS. typhimuriumpeptide-spectra using only theE. coligenome in substitution-tolerant database searching. Overall, 64.1% of library peptides were correctly identified. We observed a wide range of identification efficiencies based on the specific AAS, but no inherent bias from stoichiometry of the substitution. Short peptides and substitutions near peptide termini, which require specific diagnostic ions for unambiguous identification, are matched with below-average frequency. We also identified “scissor substitutions” that gain or lose protease cleavage sites. Although scissor substitutions are chemically distinct from the genomic peptide, they had poor identification efficiency. This ground-truth AAS library identifies multiple sources of bias in AAS peptide-spectra identification and sets expectations for the application of shotgun proteomics to testing AAS hypotheses.Significance statementHigh-fidelity decoding of the genome is essential for life. Mistranslation leads to amino acid substitutions, which can disrupt protein folding and function, and impact cell fitness. Detection of mistranslated protein products necessitates robust and non-biased approaches. Proteomics is a promising solution, but identifying non-genomic peptide-spectra is a severe bioinformatics challenge. We created a ground-truth library of substituted amino acid peptides by mixing two closely related bacteria in a single sample. We quantitatively defined the degree to which informatics could correctly distinguish substituted peptides when single-organism databases are present. This approach defines intrinsic and informatics limits in substitution detection in shotgun proteomics and identifies previously overlooked challenges with identifying “scissor substitutions”.
MELISSA: Semi-Supervised Embedding for Protein Function Prediction Across Multiple Networks
Authors: Wu Kaiyi , Zhou Di , Slonim Donna , Hu Xiaozhe , Cowen Lenore 
Published: August 2023

AbstractMotivationSeveral popular methods exist to predict function from multiple protein-protein association networks. For example, both the Mashup algorithm, introduced by Cho, Peng and Berger, and deepNF, introduced by Gligorijević, Barotand, and Bonneau, analyze the diffusion in each network first, to characterize the topological context of each node. In Mashup, the high-dimensional topological patterns in individual networks are canonically represented using low-dimensional vectors, one per gene or protein, to yield the multi-network embedding. In deepNF, a multimodal autoencoder is trained to extract common network features across networks that yield a low-dimensional embedding. Neither embedding takes into account known functional labels; rather, these are then used by the machine learning methods applied after embedding.ResultsWe introduce MELISSA (MultiNetwork Embedding with Label Integrated Semi-Supervised Augmentation) which incorporates functional labels in the embedding stage. The function labels induce sets of “must link” and “cannot link” constraints which guide a further semi-supervised dimension reduction to yield an embedding that captures both the network topology and the information contained in the annotations. We find that the MELISSA embedding improves on both the Mashup and deepNF embeddings in creating more functionally enriched neighborhoods for predicting GO labels for multiplex association networks in both yeast and humans.AvailabilityMELISSA is available athttps://github.com/XiaozheHu/melissa
Role of Adenosine Deaminase in Prostate Cancer Progression
Authors: Charles Christy , Lloyd Stacy M. , Piyarathna Danthasinghe Waduge Badrajee , Gohlke Jie , Rasaily Uttam , Putluri Vasanta , Simons Brian W. , Zaslavsky Alexander , Nallandhighal Srinivas , Palanisamy Nallasivam , Navone Nora , Jones Jeffrey A. , Ittmann Michael M. , Putluri Nagireddy , Rowley David R. , Salami Simpa S. , Palapattu Ganesh S. , Sreekumar Arun 
Published: August 2023

AbstractProstate cancer (PCa) is the second most common cancer and constitutes about 14.7% of total cancer cases. PCa is highly prevalent and more aggressive in African American (AA) men when compared to European-American (EA) men. PCa tends to be a highly heterogeneous malignancy with a complex biology that is not fully understood. We use metabolomics as a tool to understand the mechanisms behind PCa progression and disparities in its clinical outcome. A key enzyme in the purine metabolic pathway, Adenosine deaminase (ADA) was found upregulated in PCa. ADA was also associated with higher-grade PCa and poor disease-free survival. The inosine-to-adenosine ratio which is a surrogate for ADA activity was high in the urine of PCa patients and higher in AA PCa compared to EA PCa. To understand the significance of high ADA in PCa, we established ADA overexpression models and performed various in vitro and in vivo studies. Our studies have revealed that an acute increase in the expression of ADA during later stages of tumor development enhances in vivo growth in multiple pre-clinical models. Further analysis reveals that this tumor growth could be driven by the activation of mTOR signaling. Chronic ADA overexpression shows alterations in the cells’ adhesion machinery and a decrease in the adhesion potential of the cells to the extracellular matrix in vitro. Loss of cell-matrix interaction is critical for metastatic dissemination, suggestive of ADA’s role in promoting metastasis. This is consistent with the association of higher ADA expression with higher-grade tumors and poor patient survival. Overall, our findings suggest that increased ADA expression may promote PCa progression, specifically tumor growth and metastatic dissemination.
Environment predicts the maintenance of reproductive isolation in a mosaic hybrid zone of rubber rabbitbrush
Authors: Faske Trevor M. , Agneray Alison C. , Jahner Joshua P. , Osuna-Mascaró Carolina , Sheta Lana M. , Richardson Bryce A. , Leger Elizabeth A. , Parchman Thomas L. 
Published: August 2023

AbstractWidely distributed plants of western North America experience divergent selection across environmental gradients, have complex histories shaped by biogeographic barriers and distributional shifts, and often illustrate continuums of reproductive isolation. Rubber rabbitbrush (Ericameria nauseosa) is a foundational shrub species that occurs across diverse environments of western North America. Its remarkable phenotypic diversity is currently ascribed to two subspecies –E. n. nauseosaandE. n. consimilis –and 22 named varieties. We analyzed how genetic variation is partitioned across subspecies, varieties, and environment using high throughput sequencing of reduced representation libraries. We found clear evidence for divergence between the two subspecies, despite largely sympatric distributions. Numerous locations exhibiting admixed ancestry were not geographically localized but were widely distributed across a mosaic hybrid zone. The occurrence of hybrid and subspecific ancestries was strongly predicted by environmental variables as well as the proximity to major ecotones between ecoregions. Although this repeatability illustrates the importance of environmental factors in shaping reproductive isolation, variability in the outcomes of hybridization also indicated these factors likely differ across ecological contexts. There was mixed evidence for the evolutionary cohesiveness of varieties, but several genetically distinct and narrow endemic varieties exhibited admixed subspecific ancestries, hinting at the possibility for transgressive hybridization to contribute to phenotypic novelty and the colonization of new environments inE. nauseosa.
The resolution of face perception varies systematically across the visual field
Authors: Morsi Annie Y. , Goffaux Valérie , Greenwood John A. 
Published: August 2023

AbstractVisual abilities tend to vary predictably across the visual field – for simple low-level stimuli, visibility is better along the horizontal vs. vertical meridian and in the lower vs. upper visual field. In contrast, face perception abilities have been reported to show either distinct or entirely idiosyncratic patterns of variation in peripheral vision, suggesting a dissociation between the spatial properties of low- and higher-level vision. To assess this link more clearly, we extended methods used in low-level vision to develop an acuity test for face perception, measuring the smallest size at which facial gender can be reliably judged in peripheral vision. In 3 experiments, we show the characteristic inversion effect, with better acuity for upright faces than inverted, demonstrating the engagement of high-level face-selective processes in peripheral vision. We also observe a clear advantage for gender acuity on the horizontal vs. vertical meridian and a smaller-but-consistent lower- vs. upper-field advantage. These visual field variations match those of low-level vision, indicating that higher-level face processing abilities either inherit or actively maintain the characteristic patterns of spatial selectivity found in early vision. The commonality of these spatial variations throughout the visual hierarchy means that the location of faces in our visual field systematically influences our perception of them.
Changes in searching behaviour of CSL transcription complexes in Notch active conditions
Authors: Baloul Sarah , Roussos Charalambos , Gomez-Lamarca Maria , Muresan Leila , Bray Sarah 
Published: August 2023

SummaryDuring development cells receive a variety of signals, which are of crucial importance to their fate determination. One such source of signal is the Notch signalling pathway, where Notch activity regulates expression of target genes through the core transcription factor CSL. To understand changes in transcription factor behaviour that lead to transcriptional changes in Notch active cells, we have probed CSL behaviours in real time, usingin vivoSingle Molecule Localisation Microscopy. Trajectory analysis reveals that Notch-On conditions increase the fraction of bound CSL molecules, but also the proportion of molecules with exploratory behaviours. These properties are shared by the co-activator Mastermind. Furthermore, both CSL and Mastermind, exhibit characteristics of local exploration near a Notch target locus. A similar behaviour is observed for CSL molecules diffusing in the vicinity of other bound CSL clusters. We suggest therefore that CSL acquires an exploratory behaviour when part of the activation complex, favouring local searching and retention close to its target enhancers. This change explains how CSL can efficiently increases its occupancy at target sites in Notch-ON conditions.
Elucidating the complex membrane binding of a protein with multiple anchoring domains
Authors: Madsen Jesper J. , Ohkubo Y. Zenmei 
Published: August 2023

ABSTRACTMembrane binding is a crucial mechanism for many proteins, but understanding the specific interactions between proteins and membranes remains a challenging endeavor. Coagulation factor Va (FVa) is a large protein whose membrane interactions is complicated due to the presence of multiple anchoring domains that individually can bind to lipid membranes. Using molecular dynamics simulations, we investigate the membrane binding of FVa and identify the key mechanisms that govern its interaction with membranes. Our results reveal that can FVa either adopt an upright or a tilted molecular orientation upon membrane binding. We further find that the domain organization of FVa deviates (sometimes significantly) from its crystallographic reference structure, and that the molecular orientation of the protein matches with domain reorganization to align the C2 domain toward its favored membrane-normal orientation. We identify specific amino acid residues that exhibit contact preference with phosphatidylserine lipids over phosphatidylcholine lipids, and we observe that mostly electrostatic effects contribute to this preference. The observed lipid-binding process and characteristics, specific to FVa or common among other membrane proteins, in concert with domain reorganization and molecular tilt, elucidate the complex membrane binding dynamics of FVa and provide important insights into the molecular mechanisms of protein-membrane interactions.
Single-cell profiling uncovers regulatory programs of pathogenic Th2 cells in allergic asthma
Authors: Khan Matarr , Alteneder Marlis , Reiter Wolfgang , Krausgruber Thomas , Dobnikar Lina , Madern Moritz , Waldherr Monika , Bock Christoph , Hartl Markus , Ellmeier Wilfried , Henriksson Johan , Boucheron Nicole 
Published: August 2023

AbstractLung pathogenic T helper type 2 (pTh2) cells are important drivers of allergic asthma, but fundamental questions remain regarding their regulation and heterogeneity. The differentiation and effector functions of immune cells are tightly regulated by epigenetic processes. Histone deacetylase 1 (HDAC1) is an important epigenetic regulator of T cells, however, its role in pTh2 cells is yet to be determined. Here we investigate immune regulation in allergic asthma by single-cell RNA sequencing (scRNA-seq) in mice challenged with house dust mite, in the presence and absence of HDAC1 function. Our analyses reveal two distinct subsets of lung pTh2 cells: pathogenic effector Th2 (peTh2) and pathogenic Th2 tissue-resident memory (Th2 Trm) cells. Both pTh2 cell subsets are highly proinflammatory and exhibit distinct transcriptional and phenotypic signatures as compared with other lung Th subsets. Based on our scRNA-seq analysis, we identify conditions to generate pTh2 cellsin vitroand confirm that thesein vitrogenerated pTh2 cells have a similar transcriptional profile as lung peTh2 cells. Using our newin vitromodel, we demonstrate that the p38 mitogen-activated protein kinase pathway is critical for interleukin-5 (IL-5) and IL-13 expression in pTh2 cells. Our data further underline the importance of HDAC1 in limiting the pathogenicity of lung andin vitropTh2 cells and in the formation of lung Th2 Trm cells. In summary, we have generated novel insights into pTh2 cell biology and established a newin vitromodel for investigating pTh2 cells that will be useful for discovering molecular mechanisms involved in pTh2-mediated allergic asthma.