bluuebunny/crossref_metadata_2025_split huggingface dataset:
GraphPart: Homology partitioning for biological sequence analysis
Authors: Teufel Felix , Gíslason Magnús Halldór , Almagro Armenteros José Juan , Johansen Alexander Rosenberg , Winther Ole , Nielsen Henrik 
Published: April 2023

AbstractWhen splitting biological sequence data for the development and testing of predictive models, it is necessary to avoid too closely related pairs of sequences ending up in different partitions. If this is ignored, performance estimates of prediction methods will tend to be exaggerated. Several algorithms have been proposed for homology reduction, where sequences are removed until no too closely related pairs remain. We present GraphPart, an algorithm for homology partitioning, where as many sequences as possible are kept in the dataset, but partitions are defined such that closely related sequences always end up in the same partition. Evaluation of GraphPart on Protein, DNA and RNA datasets shows that it is capable of retaining a larger number of sequences per dataset, while providing homology separation quality on par with reduction approaches.
Feasibility in MacArthur’s Consumer-Resource Model
Authors: Aparicio Andrea , Wang Tong , Saavedra Serguei , Liu Yang-Yu 
Published: April 2023

AbstractFinding the conditions that ensure the survival of species has occupied ecologists for decades. Theoretically, for mechanistic models such as MacArthur’s consumer-resource model, most of the efforts have concentrated on proving the stability of an equilibrium assuming that it is feasible, but overlooking the conditions that ensure its feasibility. Here we address this gap by finding the range of conditions that lead to a feasible equilibrium of MacArthur’s consumer-resource model and study how changes in the system’s structural and parametric properties affect those ranges. We characterize the relationship between the loss of feasibility and the increase in complexity (measured by the system’s richness and connectance) by a power law that can be extended to random competition matrices. Focusing on the pool of consumers, we find that while the feasibility of the entire system decreases with the size of the pool, the expected fraction of feasible consumers increases —safety in consumer numbers. Focusing on the pool of resources, we find that if resources grow linearly, the larger the pool of resources, the lower the feasibility of the system and the expected fraction of feasible consumers —danger in resource numbers. However, if resources grow logistically, this pattern is reversed with a sublinear increase in feasibility, as it has been previously reported in experimental work. This work provides testable predictions for consumer-resource systems and is a gateway to exploring feasibility in other mechanistic models.
Total Chemical Synthesis of Glycosylated TREM2 Ectodomain
Authors: Wijegunawardena Gayani , Castillo Erika , Henrickson Brandy , Davis Regan , Condello Carlo , Wu Haifan 
Published: April 2023

ABSTRACTMutations in a microglia-associated geneTREM2increase the risk of Alzheimer’s disease. Currently, structural and functional studies of TREM2 mainly rely on recombinant TREM2 proteins expressed from mammalian cells. However, using this method, it is difficult to achieve site-specific labeling. Here we present the total chemical synthesis of the 116 amino-acid TREM2 ectodomain. Rigorous structural analysis ensured correct structural fold after refolding. Treating microglial cells with refolded synthetic TREM2 enhanced microglial phagocytosis, proliferation, and survival. We also prepared TREM2 constructs with defined glycosylation patterns and found that glycosylation at N79 is critical to the thermal stability of TREM2. This method will provide access to TREM2 constructs with site-specific labeling, such as fluorescent labeling, reactive chemical handles, and enrichment handles, to further advance our understanding of TREM2 in Alzheimer’s disease.
Sexual Dimorphism in VEMP peak to trough Latency
Authors: Gattie Max , Lieven Elena V. M. , Kluk Karolina 
Published: April 2023

AbstractThe cervical vestibular-evoked myogenic potential (VEMP) was assessed in 24 women and 24 men having a mean age of 19.5 years (SD 0.7). Whilst there was no group difference in VEMP peak to trough (p1-n1) amplitude, VEMP p1-n1 latency was found to be shorter for women than for men by 2.4 ms (95% CI [–0.9, –3.9], chi squared (1) 9.6, p = 0.0020). This equates to 21% of the mean 11.4 ms VEMP p1-n1 latency across women and men. It is a reversal of findings in several prior studies, which are reviewed here. Statistical modelling based on the current study suggests some prior studies were underpowered to detect a sex difference in VEMP latency. Possible causes for sex difference in VEMPs are discussed. Candidate explanations include head resonance, superposition of motor unit action potentials and influence of sex hormones. These explanations are not mutually exclusive, and multiple factors may contribute to difference in VEMP measurement between women and men. This study used a methodology developed in Gattie et al. (2021), which addresses sound exposure concerns with the high amplitude air conducted stimuli necessary to evoke a VEMP response. It is suggested that body conducted stimuli may be preferable for VEMP testing in which ear-specific information is not required.
I-Spin live: An open-source software based on blind-source separation for real-time decoding of motor unit activity in humans
Authors: Rossato Julien , Hug François , Tucker Kylie , Gibbs Ciara , Lacourpaille Lilian , Farina Dario , Avrillon Simon 
Published: April 2023

AbstractDecoding the activity of individual neural cells during natural behaviours allows neuroscientists to study how the nervous system generates and controls movements. Contrary to other neural cells, the activity of spinal motor neurons can be determined non-invasively (or minimally invasively) from the decomposition of electromyographic (EMG) signals into motor unit firing activities. For some interfacing and neuro-feedback investigations, EMG decomposition needs to be performed in real-time. Here, we introduce an open-source software that performs real-time decoding of motor neurons using a blind-source separation approach for multichannel EMG signal processing. Separation vectors (motor unit filters) are optimised for each motor unit from baseline contractions and then re-applied in real-time during test contractions. In this way, the firing activity of multiple motor neurons can be provided through different forms of visual feedback. We provide a complete framework with guidelines and examples of recordings to guide researchers who aim to study movement control at the motor neuron level. We first validated the software with synthetic EMG signals generated during a range of isometric contraction patterns. We then tested the software on data collected using either surface or intramuscular electrode arrays from five lower limb muscles (gastrocnemius lateralis and medialis, vastus lateralis and medialis, and tibialis anterior). We assessed how the muscle or variation of contraction intensity between the baseline contraction and the test contraction impacted the accuracy of the real-time decomposition. This open-source software provides a set of tools for neuroscientists to design experimental paradigms where participants can receive real-time feedback on the output of the spinal cord circuits.
SUMOylation of Bonus, theDrosophilahomolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes
Authors: Godneeva Baira , Ninova Maria , Fejes Tóth Katalin , Aravin Alexei A. 
Published: April 2023

AbstractThe conserved family of Transcription Intermediary Factors (TIF1) proteins consists of key transcriptional regulators that control transcription of target genes by modulating chromatin state. Unlike mammals that have four TIF1 members,Drosophilaonly encodes one member of the family, Bonus. Bonus has been implicated in embryonic development and organogenesis and shown to regulate several signaling pathways, however, its targets and mechanism of action remained poorly understood. We found that knockdown of Bonus in early oogenesis results in severe defects in ovarian development and in ectopic expression of genes that are normally repressed in the germline, demonstrating its essential function in the ovary. Recruitment of Bonus to chromatin leads to silencing associated with accumulation of the repressive H3K9me3 mark. We show that Bonus associates with the histone methyltransferase SetDB1 and the chromatin remodeler NuRD and depletion of either component releases Bonus-induced repression. We further established that Bonus is SUMOylated at a single site at its N-terminus that is conserved among insects and this modification is indispensable for Bonus’s repressive activity. SUMOylation influences Bonus’s subnuclear localization, its association with chromatin and interaction with SetDB1. Finally, we showed that Bonus SUMOylation is mediated by the SUMO E3-ligase Su(var)2-10, revealing that although SUMOylation of TIF1 proteins is conserved between insects and mammals, both the mechanism and specific site of modification is different in the two taxa. Together, our work identified Bonus as a regulator of tissue-specific gene expression and revealed the importance of SUMOylation as a regulator of complex formation in the context of transcriptional repression.
Characterizing the mechanical properties of low-profile prosthetic feet
Authors: Tacca Joshua R. , Colvin Zane A. , Grabowski Alena M. 
Published: April 2023

AbstractPassive-elastic prosthetic feet are manufactured with different numerical stiffness categories that are prescribed based on the body mass and activity level of the user, but the mechanical properties, such as the stiffness values and hysteresis are not typically reported by the manufacturer. Since the mechanical properties of passive-elastic prosthetic feet can affect the walking biomechanics of people with transtibial or transfemoral amputation, characterizing these properties would provide objective values for comparison and aid the prescription of prosthetic feet. Therefore, we characterized the axial stiffness values, torsional stiffness values, and hysteresis of 33 different categories and sizes of a commercially available passive-elastic prosthetic foot model, the Össur low-profile (LP) Vari-flex with and without a shoe. We measured axial stiffness from compression and torsional stiffness from dorsiflexing and plantarflexing the prostheses. In general, a greater numerical prosthetic foot stiffness category resulted in increased heel, midfoot, and forefoot axial stiffness values, increased plantarflexion and dorsiflexion torsional stiffness values, and decreased heel, midfoot, and forefoot hysteresis. Moreover, a greater prosthetic foot size resulted in decreased heel, midfoot, and forefoot axial stiffness values, increased plantarflexion and dorsiflexion torsional stiffness values, and decreased heel and midfoot hysteresis. Finally, adding a shoe to the LP Vari-flex prosthetic foot resulted in decreased heel and midfoot axial stiffness values, decreased plantarflexion torsional stiffness values, and increased heel, midfoot, and forefoot hysteresis. In addition, we found that the force-displacement and torque-angle relationships were better described by curvilinear than linear equations. Ultimately, our results can be used to objectively compare LP Vari-flex prosthetic feet to other prosthetic feet in order to inform their prescription and design and use by people with a transtibial or transfemoral amputation.
Advances on sparse Dynamic Scanning in Spectromicroscopy through Compressive Sensing
Authors: Kourousias George , Billè Fulvio , Ippoliti Matteo , Guzzi Francesco , Bonanni Valentina , Gianoncelli Alessandra 
Published: April 2023

AbstractScanning microscopies and spectroscopies like X-ray Fluorescence (XRF), Scanning Transmission X-ray Microscopy (STXM), and Ptychography are of very high scientific importance as they can be employed in several research fields. Methodology and technology advances aim at analysing larger samples at better resolution, improved sensitivities and higher acquisition speeds. The frontiers of those advances are on detectors, radiation sources, motors, but also on acquisition and analysis software together with general methodology improvements. We’ve e recently introduced and fully implemented on a soft X-ray microscopy beamline an intelligent scanning methodology based on compressive sensing. This demonstrated sparse low energy XRF scanning of dynamically chosen regions of interest in combination with STXM. It resulted in a sparse megapixel-rage low energy XRF spectroimaging through dynamic scanning that was previously not feasible. This research has been further developed and has been applied in scientific applications in biology. The developments are mostly on the dynamic triggering decisional mechanism in order to incorporate modern Machine Learning and real-time XRF fitting but also on the suitable integration of the method in the control system making it available for other beamlines and imaging techniques. On the applications front, the method was successfully used on different samples, from lung and ovarian human tissues to plant root sections. This manuscript introduces the latest advances of the method and demonstrates applications in life and environmental sciences. Finally it highlights an auxiliary development of a mobile application that assists the selection of specific regions of interest in an easy way.
Loss of presenilin-1 in smooth muscle cells ameliorates elastin aortopathy
Authors: Saito Junichi , Dave Jui M. , Lau Freddy Duarte , Greif Daniel M. 
Published: April 2023

AbstractSmooth muscle cell (SMC) accumulation is central to the pathogenesis of elastin-defective arterial diseases, such as atherosclerosis, pulmonary hypertension and supravalvular aortic stenosis (SVAS). We previously demonstrated that elastin insufficiency activates the Notch pathway in aortic SMCs, resulting in hypermuscularization. Activation of Notch is catalyzed by the enzyme gamma-secretase, but the role of specific catalytic subunits PSEN-1 or PSEN-2 in elastin aortopathy is not defined. This study utilizes genetic approaches to query the role of PSEN-1/2 in the pathogenesis of elastin mutant mice, which model human SVAS. Although endothelial cell-specificPsen1deletion does not improve elastin aortopathy, deletion of eitherPsen1in SMCs orPsen2globally attenuates Notch downstream gene expression and SMC proliferation, mitigating aortic disease. With SMC-specificPsen1deletion in elastin nulls, these rescue effects are more robust and in fact, survival is increased. On the background ofPsen1deletion in SMCs, globalPsen2deletion yields additional benefits in regard to elastin aortopathy. Finally, SMC deletion ofPsen1also attenuates hypermuscularization in newborns heterozygous for the elastin null gene, which genetically mimics SVAS. Taken together, these findings put forth SMC PSEN-1 as a potential therapeutic target in elastin aortopathy.
Bumble bees (Bombus terrestris) use time-memory to associate reward with color and time of day
Authors: Gonulkirmaz-Cancalar Ozlem , Shertzer Oded , Bloch Guy 
Published: April 2023

AbstractCircadian clocks regulate ecologically important complex behaviors in honey bees but it is not clear to what extent these observations can be extended to other species of bees. One key behavior is time-memory allowing foraging bees to precisely time flower visitation to periods of maximal pollen or nectar availability and reducing the costs of arriving at a flower patch at the wrong time. It is unclear whether other bees such as bumble bees, who live in smaller societies and forage over shorter distances than honey bees, can similarly associate a reward with time of day. We trained individually marked bumble bee (Bombus terrestris) workers to forage for sugar syrup in a flight cage with yellow or blue feeders rewarding either during the morning or evening. After a two-weeks training session, we recorded all visitations to colored feeders filled with only water. We repeated this experiment twice, with different colonies. We found that bees tended to show higher foraging activity during the morning and evening training sessions compared to other times during the day. Trained bees were more likely to visit feeders with colors rewarding compared to non-rewarding at the same time of day during the training sessions and with relatively fewer mistakes. Our findings lend credence to the hypothesis that efficient time-memory is not limited to species such as honey bees that evolved sophisticated social foraging behaviors over large distances.
Conceptual representations in the default, control and attention networks are task-dependent and cross-modal
Authors: Kuhnke Philipp , Kiefer Markus , Hartwigsen Gesa 
Published: April 2023

AbstractConceptual knowledge is central to human cognition. Neuroimaging studies suggest that conceptual processing involves modality-specific and multimodal brain regions in a task-dependent fashion. However, it remains unclear (1) to what extent conceptual feature representations are also modulated by the task, (2) whether conceptual representations in multimodal regions are indeed cross-modal, and (3) how the conceptual system relates to the large-scale functional brain networks. To address these issues, we conducted multivariate pattern analyses on fMRI data. 40 participants performed three tasks—lexical decision, sound judgment, and action judgment—on written words. We found that (1) conceptual feature representations are strongly modulated by the task, (2) conceptual representations in several multimodal regions are cross-modal, and (3) conceptual feature retrieval involves the default, frontoparietal control, and dorsal attention networks. Conceptual representations in these large-scale networks are task-dependent and cross-modal. Our findings support theories that assume conceptual processing to rely on a flexible, multi-level architecture.
Natural forgetting reversibly modulates engram expression
Authors: O’Leary James D. , Bruckner Rasmus , Autore Livia , Ryan Tomás J. 
Published: April 2023

SummaryMemories are stored as ensembles of engram neurons and their successful recall involves the reactivation of these cellular networks. However, significant gaps remain in connecting these cell ensembles with the process of forgetting. Here, we utilized a mouse model of object memory and investigated the conditions in which a memory could be preserved, retrieved, or forgotten. Direct modulation of engram activity via optogenetic stimulation or inhibition either facilitated or prevented the recall of an object memory. In addition, through behavioral and pharmacological interventions, we successfully prevented or accelerated forgetting of an object memory. Finally, we showed that these results can be explained by a computational model in which engrams that are subjectively less relevant for adaptive behavior are more likely to be forgotten. Together, these findings suggest that forgetting may be an adaptive form of engram plasticity which allows engrams to switch from an accessible state to an inaccessible state.
Tuning Minimum-Norm regularization parameters for optimal MEG connectivity estimation
Authors: Vallarino Elisabetta , Hincapié Ana Sofia , Jerbi Karim , Leahy Richard , Pascarella Annalisa , Sorrentino Alberto , Sommariva Sara 
Published: April 2023

AbstractThe accurate characterization of cortical functional connectivity from Magnetoencephalography (MEG) data remains a challenging problem due to the subjective nature of the analysis, which requires several decisions at each step of the analysis pipeline, such as the choice of a source estimation algorithm, a connectivity metric and a cortical parcellation, to name but a few. Recent studies have emphasized the importance of selecting the regularization parameter in minimum norm estimates with caution, as variations in its value can result in significant differences in connectivity estimates. In particular, the amount of regularization that is optimal for MEG source estimation can actually be suboptimal for coherence-based MEG connectivity analysis. In this study, we expand upon previous work by examining a broader range of commonly used connectivity metrics, including the imaginary part of coherence, corrected imaginary part of Phase Locking Value, and weighted Phase Lag Index, within a larger and more realistic simulation scenario. Our results show that the best estimate of connectivity is achieved using a regularization parameter that is 1 or 2 orders of magnitude smaller than the one that yields the best source estimation. This remarkable difference may imply that previous work assessing source-space connectivity using minimum-norm may have benefited from using less regularization, as this may have helped reduce false positives. Importantly, we provide the code for MEG data simulation and analysis, offering the research community a valuable open source tool for informed selections of the regularization parameter when using minimum-norm for source space connectivity analyses.HighlightsThe regularization parameter of the Minimum Norm Estimate of neural activity impacts connectivity estimationWe study empirically the optimal parameter for connectivity estimation using realistic synthetic datasetsWe find the optimal parameter for connectivity estimation is systematically smaller than the optimal parameter for source imaging; different connectivity metrics yield the same resultCode and data are available open source.
A transient dermal niche and dual epidermal programs underlie sweat gland development
Authors: Dingwall Heather L. , Tomizawa Reiko R. , Aharoni Adam , Hu Peng , Qiu Qi , Kokalari Blerina , Martinez Serenity M. , Donahue Joan C. , Aldea Daniel , Mendoza Meryl , Glass Ian A. ,   Birth Defects Research Laboratory (BDRL), Wu Hao , Kamberov Yana G. 
Published: April 2023

AbstractEccrine glands are mammalian skin appendages indispensable for human thermoregulation. Like all skin-derived appendages, eccrine glands form from multipotent progenitors in the basal skin epidermis. It remains unclear how epidermal progenitors progressively specialize to specifically form eccrine glands, precluding efforts to regenerate these vital organs. Herein, we applied single nucleus transcriptomics to compare the expression content of wildtype, eccrine-forming mouse skin to that of mice harboring a skin-specific disruption ofEngrailed 1 (En1), a transcription factor that promotes the formation of eccrine glands in both humans and mice. We identify two concurrent epidermal transcriptomes in the earliest eccrine anlagen: a predominant transcriptome that is shared with hair follicles, and a vastly underrepresented transcriptome that isEn1-dependent and eccrine-specific. We demonstrate that differentiation of the eccrine anlage requires the induction of a transient and transcriptionally unique dermal niche that forms around each developing gland in humans and mice. Our study defines the transcriptional determinants underlying eccrine identity in the epidermis and uncovers the dermal niche required for eccrine developmental progression. By identifying these defining components of the eccrine developmental program, our findings set the stage for directed efforts to regenerate eccrine glands for comprehensive skin repair.