bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural Speech-Tracking During Selective Attention: A Spatially Realistic Audiovisual Study
Authors: Har-shai Yahav Paz , Rabinovitch Eshed , Korisky Adi , Vaknin Harel Renana , Bliechner Martin , Zion Golumbic Elana 
Published: December 2023

AbstractPaying attention to a target talker in multi-talker scenarios is associated with its more accurate neural-tracking relative to competing non-target speech. This “neural-bias” to target speech has largely been demonstrated in experimental setups where target and non-target speech are acoustically controlled and interchangeable. However, in real-life situations this is rarely the case. For example, listeners often look at the talker they are paying attention to while non-target speech is heard (but not seen) from peripheral locations. To enhance the ecological-relevance of attention research, here we studied whether neural-bias towards target speech is observed in a spatially realistic audiovisual context, and how this is affected by switching the identity of the target talker.Group-level results show robust neural-bias towards target speech, an effect that persisted and generalized after switching the identity of the target talker. In line with previous studies, this supports the utility of the speech-tracking approach for studying speech processing and attention in spatially realistic settings. However, a more nuanced picture emerges when inspecting data of individual participants. Although reliable neural speech-tracking could be established in most participants, this was not correlated with neural-bias or with behavioral performance, and >50% of participant showed similarly robust neural tracking of both target and non-target speech.These results indicate that neural-bias toward the target is not a ubiquitous, or necessary, marker of selective attention (at least as measured from scalp-EEG), and suggest that individuals diverge in their internal prioritization among concurrent speech, perhaps reflecting different listening strategies or capabilities under realistic conditions.Significance StatementThis work contributes to ongoing efforts to study the neural mechanisms involved in selective attention to speech under ecologically relevant conditions, emulating the type of speech materials, multisensory experience, and spatial realism of natural environments. Group-level results show that under these more realistic conditions, the hallmark signature of selective attention – namely the modulation of sensory representation, and its robustness to switches in target-identity – is conserved, at least at the group level. At the same time, results point to an underlying diversity among participants in how that this modulation manifests, raising the possibility that differences in listening strategies, motivation or personal traits lead to differences in the way that individuals encode and process competing stimuli, under ecological conditions.
Microscopy-guided subcellular proteomic discovery by high-speed ultra-content photo-biotinylation
Authors: Chen Yi-De , Chang Chih-Wei , Cheung Chantal Hoi Yin , Chang Hsiao-Jen , Sie Yong-Da , Chung Chia-Wen , Huang Chun-Kai , Huang Chien-Chang , Chong Weng Man , Liu You-Pi , Lin Yu-Chih , Kai Hsiang-Ju James , Wang Pei-Jie , Liao Jung-Chi 
Published: December 2023

AbstractMicroscopy-guided proteomics at an organelle-dimension resolution is desired for revealing unknown protein constituents at specific disease- or functional-associated regions at the molecular-molecular interactions level. Here, we achieve protein spatial purification by introducing a firmware-integrated microscopy platform that triggersin situsubcellular photo-biotinylation of proteins at user-defined regions of interest (ROIs) one field of view (FOV) at a time for thousands of FOVs fully automatically. An illumination pattern at the analogous ROIs of each FOV is calculated on the fly by either machine learning or traditional image processing. Photoactivatable amino acid crosslinkers are activated by a two-photon focal light one spot at a time at a sub-millisecond illumination duration per spot. Imaging, pattern generation, targeted illumination, and FOV movement are coordinated and cycled with high-speed mechatronic control to complete illumination on millions of ROI spots within hours. Once enough proteins are biotinylated in a cell or tissue sample, the sample is scraped and lysed, and avidin pulldown is used to enrich proteins to achieve spatial protein scooping at a 240-nm precision. Subsequent LC-MS/MS is implemented to reveal the subcellular proteome in high sensitivity, specificity, and resolution. Using this technology termed optoproteomics, we have revealed novel stress granule-localized and amyloid β-localized proteins validated by immunostaining. Together, spatial purification by ultra-content, high-speed microscopy-targeted photo-biotinylation enables unprecedented subcellular spatial proteomics discovery in any microscopically recognizable regions.
A Modified Tseng Algorithm Approach to Restoring Thoracic Diseases’ Computerized Tomography Images
Authors: Umar Huzaifa , Adamu Abubakar , Hijaz Ahmad , Ozsahin Dilber Uzun 
Published: December 2023

AbstractIt is well-known that the Tseng algorithm and its modifications have been successfully employed in approximating zeros of the sum of monotone operators. In this study, we restored various thoracic diseases’ computerized tomography (CT) images, which were degraded with a known blur function and additive noise, using a modified Tseng algorithm. The test images used in the study depict calcification of the Aorta, Subcutaneous Emphysema, Tortuous Aorta, Pneumomediastinum, and Pneumoperitoneum. Additionally, we employed well-known image restoration tools to enhance image quality and compared the quality of restored images with the originals. Finally, the study demonstrates the potential to advance monotone inclusion problem-solving, particularly in the field of medical image recovery.
The placental protein NRK promotes cell death through its plasma membrane-localizing CNH domain
Authors: Lestari Beni , Soda Kohei , Moritsugu Kei , Kidera Akinori , Suenaga Yusuke , Hippo Yoshitaka , Meiyanto Edy , Komada Masayuki , Wahyuningsih Mae Sri Hartati , Fukushima Toshiaki 
Published: December 2023

AbstractPlacental development is regulated by the balance between cell proliferation and death. The placental protein NRK (NIK-related kinase) plays a role in preventing excessive placenta growth. We previously demonstrated that NRK underwent rapid molecular evolution in the ancestor of placental mammals and acquired the functional regions, including the phospholipid-binding citron homology (CNH) domain, by which NRK inhibits cell proliferation. NRK is also potentially responsible for cell death; caspases cleave NRK during apoptosis, releasing theC-terminal fragment that promotes cell death. Here, we explored the molecular mechanisms underlying the cell death-promoting effects of NRK. Our experimental data using HeLa, placenta trophoblast BeWo (human), and Rcho-1 (rat) cells indicated that the CNH domain of NRK was required and sufficient to promote cell death.In vitroandin silicostudies showed the NRK CNH domain bound to phospholipids via its polybasic clusters and remains at the plasma membrane (PM) during apoptosis. Evolutional analyses indicated that these clusters formed in the ancestor of placental mammals. Mutations in these clusters (CNH-18A) hindered the cell death-promoting activity of the CNH domain. We concluded that NRK promotes cell death through its plasma membrane-localizing CNH domain and suggested its active role in PM-associated events during cell death.
p23-FKBP51 chaperone complex regulates tau aggregation
Authors: Chakraborty Pijush , Zweckstetter Markus 
Published: December 2023

AbstractThe pathological deposition of tau into insoluble amyloid fibrils is a pathological hallmark of tauopathies. Molecular chaperones are important cellular factors contributing to the regulation of tau misfolding and aggregation. Here we reveal an Hsp90-independent modulation of tau aggregation by a molecular complex of the two Hsp90 co-chaperones p23 and FKBP51. Integrating NMR spectroscopy, SAXS, molecular docking, and site-directed mutagenesis we reveal the structural basis of the p23-FKBP51 complex. We show that p23 specifically recognizes the TPR domain of FKBP51 and interacts with tau through its C-terminal disordered tail. We further show that the p23-FKBP51 complex binds tau to form a dynamic p23-FKBP51-tau trimeric complex that inhibits tau aggregation and thus may counteract Hsp90-FKBP51 mediated toxicity. Taken together, our findings reveal a co-chaperone mediated Hsp90-independent chaperoning of tau protein.
A yeast love triangle: multiple hybridizations shape genome evolution in thePichia cactophilaspecies complex
Authors: Mixão Verónica , Saus Ester , Hagen Ferry , Boekhout Teun , Stevens Ryan R. , Gabaldón Toni 
Published: December 2023

AbstractHybrids are chimeric organisms carrying genetic material from at least two divergent parental lineages. Hybridization can contribute to the emergence of novel lineages with unique phenotypic traits that may facilitate their adaptation to new environments. In recent years, genomic analyses have revealed the hybrid nature of several opportunistic human pathogenic yeasts. One of them isCandida inconspicua,a member of thePichia cactophilaspecies complex, for which all sequenced strains are hybrids isolated from Europe with so far unknown parentals. It has been recently proposed thatC. inconspicuaandP. cactophilas.s. should be ranked as the same species due to their genetic similarity. To obtain a better understanding of the evolution of this clade, we sequenced the genomes of theP. cactophilatype strain, of its close-relativePichia pseudocactophila, and of a putativeC. inconspicuaclinical isolate from Alaska and compared them with the previously sequenced genomes ofPichia norvegensis, C. inconspicuaand the recently describedPichia galeolata. Our results show evidence for the existence of distinct hybrid lineages within this clade and suggest an intricate scenario of recurrent hybridizations in this species complex, some of them giving rise to lineages with the ability to infect humans. Given their different hybridization histories, we propose thatC. inconspicua, P. cactophila,and the new clinical isolate from Alaska should represent three distinct species and suggest the namePichia alaskaensisfor the new taxon. Moreover, the nameC. inconspicuais recombined in the genusPichiaasP. inconspicua. Our results clarify the evolutionary relationships within theP. cactophilaspecies complex and underscore the importance of non-vertical evolution.
From Inhibition to Excitation and Why: The Role of Temporal Urgency in Modulating Corticospinal Activity
Authors: McInnes Aaron N. , Smithers Benjamin , Lipp Ottmar V. , Tresilian James R. , Vallence Ann-Maree , Rothwell John C. , Marinovic Welber 
Published: December 2023

AbstractPrevious research on movement preparation identified a period of corticospinal suppression about 200 ms prior to movement initiation. This phenomenon has been observed for different types of motor tasks typically used to investigate movement preparation (e.g., reaction time, self-initiated, and anticipatory actions). However, we recently discovered that this phenomenon is not observed when actions must be initiated under time pressure. In the present study, we investigated urgency effects on corticospinal suppression throughout the time course of an anticipatory timing task. Participants were required to perform timing actions under two urgency scenarios, high and low, and we applied single-pulse transcranial magnetic stimulation at different times during the time course of preparation. We analysed the time course of excitability under high and low scenarios in relation to expected and actual movement onset times. Our results confirmed our earlier findings that corticospinal suppression is not observed when participants perform actions under high urgency scenarios. In addition, we found no evidence that this preparatory suppression could be shifted in time to occur later under high urgency scenarios. Moreover, we found evidence that responses prepared under high urgency are more likely to be disrupted by external events (e.g., TMS pulses). These results suggest that preparatory suppression might be a strategy employed by the central nervous system to shield motor actions from interference of external events (e.g., loud sounds) when time allows. Given these data, we propose conceptual models that could account for the absence of preparatory suppression under time pressure to act.
Comparative genomics ofCryptococcusandKwoniellareveals pathogenesis evolution and contrasting karyotype dynamics via intercentromeric recombination or chromosome fusion
Authors: Coelho Marco A. , David-Palma Márcia , Shea Terrance , Bowers Katharine , McGinley-Smith Sage , Mohammad Arman W. , Gnirke Andreas , Yurkov Andrey M. , Nowrousian Minou , Sun Sheng , Cuomo Christina A. , Heitman Joseph 
Published: December 2023

AbstractA large-scale comparative genomic analysis was conducted for the global human fungal pathogens within theCryptococcusgenus, compared to non-pathogenicCryptococcusspecies, and related species from the sister genusKwoniella. Chromosome-level genome assemblies were generated for multiple species of both genera, resulting in a dataset encompassing virtually all of their known diversity. AlthoughCryptococcusandKwoniellahave comparable genome sizes (about 19.2 and 22.9 Mb) and similar gene content, hinting at pre-adaptive pathogenic potential, our analysis found evidence in pathogenicCryptococcusspecies of specific examples of gene gain (via horizontal gene transfer) and gene loss, which might represent evolutionary signatures of pathogenic development. Genome analysis also revealed a significant variation in chromosome number and structure between the two genera. By combining synteny analysis and experimental centromere validation, we found that mostCryptococcusspecies have 14 chromosomes, whereas mostKwoniellaspecies have fewer (11, 8, 5 or even as few as 3). Reduced chromosome number inKwoniellais associated with formation of giant chromosomes (up to 18 Mb) through repeated chromosome fusion events, each marked by a pericentric inversion and centromere loss. While similar chromosome inversion-fusion patterns were observed in allKwoniellaspecies with fewer than 14 chromosomes, no such pattern was detected inCryptococcus. Instead,Cryptococcusspecies with less than 14 chromosomes, underwent chromosome reductions primarily through rearrangements associated with the loss of repeat-rich centromeres. Additionally,Cryptococcusgenomes exhibited frequent interchromosomal translocations, including intercentromeric recombination facilitated by transposons shared between centromeres. Taken together, our findings advance our understanding of genomic changes possibly associated with pathogenicity inCryptococcusand provide a foundation to elucidate mechanisms of centromere loss and chromosome fusion driving distinct karyotypes in closely related fungal species, including prominent global human pathogens.
Hippocampal sequences span experience relative to rewards
Authors: Sosa Marielena , Plitt Mark H. , Giocomo Lisa M. 
Published: December 2023

ABSTRACTHippocampal place cells fire in sequences that span spatial environments and non-spatial modalities, suggesting that hippocampal activity can anchor to the most behaviorally salient aspects of experience. As reward is a highly salient event, we hypothesized that sequences of hippocampal activity can anchor to rewards. To test this, we performed two-photon imaging of hippocampal CA1 neurons as mice navigated virtual environments with changing hidden reward locations. When the reward moved, the firing fields of a subpopulation of cells moved to the same relative position with respect to reward, constructing a sequence of reward-relative cells that spanned the entire task structure. The density of these reward- relative sequences increased with task experience as additional neurons were recruited to the reward- relative population. Conversely, a largely separate subpopulation maintained a spatially-based place code. These findings thus reveal separate hippocampal ensembles can flexibly encode multiple behaviorally salient reference frames, reflecting the structure of the experience.
Phosphatases of regenerating liver balance F-actin rearrangements during T cell activation through WD repeat containing protein 1
Authors: Aguilar-Sopeña Óscar , Carrasco-Padilla Carlos , Gomez-Moron Álvaro , Castro-Sánchez Patricia , Estarás-Hermosel Matías , Valvo Salvatore , Alegre-Gómez Sergio , Redondo-Muñoz Javier , Torres Raúl , Rodríguez-Perales Sandra , Ismail Shehab , Sánchez-Madrid Francisco , Martín-Cófreces Noa B. , Dustin Michael L. , Roda-Navarro Pedro 
Published: December 2023

AbstractPhosphatases of regenerating liver (PRLs) have been proposed to regulate actin dynamics in lymphoid cells. However, the mechanism mediating this role remained unknown. Here we showed the interaction of the PRLs with the actin regulator WD repeat containing protein 1 (WDR1). The interaction of the PRLs with WDR1 was dependent on F-actin integrity and the proper recruitment of the PRLs to cell membranes through the CAAX motif. Endogenous PRLs and WDR1 were distributed to the Immunological Synapse (IS) and perturbed expression of PRL-1 or PRL-2 by CRISPR/Cas9 mediated genome editing showed that the PRLs were required for proper distribution of WDR1 to filamentous (F)-actin at the IS. Further, perturbed expression of the PRLs or WDR1 resulted in defective IS assembly with deregulated F-actin rearrangements, altered positioning of LFA-1, and reduced IL-2 production. Interestingly, balanced expression of PRLs was required for accumulation of CD3ε at the IS and early activating signalling. We propose that PRLs regulate early T cell signalling and are required for proper F-actin dynamics by regulating the WDR1 access to F-actin networks. As a consequence, PRLs regulate LFA-1 positioning at the IS and proper cytokine secretion.
Identification of a myofibroblast differentiation program during neonatal lung development
Authors: Yin Yongjun , Koenitzer Jeffrey R. , Patra Debabrata , Dietmann Sabine , Bayguinov Peter , Hagan Andrew S. , Ornitz David M. 
Published: December 2023

AbstractAlveologenesis is the final stage of lung development in which the internal surface area of the lung is increased to facilitate efficient gas exchange in the mature organism. The first phase of alveologenesis involves the formation of septal ridges (secondary septae) and the second phase involves thinning of the alveolar septa. Within secondary septa, mesenchymal cells include a transient population of alveolar myofibroblasts (MyoFB) and a stable but poorly described population of lipid rich cells that have been referred to as lipofibroblasts or matrix fibroblasts (MatFB). Using a uniqueFgf18CreERlineage trace mouse line, cell sorting, single cell RNA sequencing, and primary cell culture, we have identified multiple subtypes of mesenchymal cells in the neonatal lung, including an immature progenitor cell that gives rise to mature MyoFB. We also show that the endogenous and targeted ROSA26 locus serves as a sensitive reporter for MyoFB maturation. These studies identify a myofibroblast differentiation program that is distinct form other mesenchymal cells types and increases the known repertoire of mesenchymal cell types in the neonatal lung.Summary StatementDuring primary alveologenesis, alveolar myofibroblasts comprise a distinct proliferative mesenchymal lineage that matures and populates emerging secondary septa.
Functional characterization of allCDKN2Amissense variants and comparison to in silico models of pathogenicity
Authors: Kimura Hirokazu , Lahouel Kamel , Tomasetti Cristian , Roberts Nicholas J. 
Published: December 2023

AbstractInterpretation of variants identified during genetic testing is a significant clinical challenge. In this study, we developed a high-throughput CDKN2A functional assay and characterized all possibleCDKN2Amissense variants. We found that 17.7% of all missense variants were functionally deleterious. We also used our functional classifications to assess the performance of in silico models that predict the effect of variants, including recently reported models based on machine learning. Notably, we found that all in silico models performed similarly when compared to our functional classifications with accuracies of 39.5-85.4%. Furthermore, while we found that functionally deleterious variants were enriched within ankyrin repeats, we did not identify any residues where all missense variants were functionally deleterious. Our functional classifications are a resource to aid the interpretation ofCDKN2Avariants and have important implications for the application of variant interpretation guidelines, particularly the use of in silico models for clinical variant interpretation.
ADMET-AI: A machine learning ADMET platform for evaluation of large-scale chemical libraries
Authors: Swanson Kyle , Walther Parker , Leitz Jeremy , Mukherjee Souhrid , Wu Joseph C. , Shivnaraine Rabindra V. , Zou James 
Published: December 2023

AbstractSummaryThe emergence of large chemical repositories and combinatorial chemical spaces, coupled with high-throughput docking and generative AI, have greatly expanded the chemical diversity of small molecules for drug discovery. Selecting compounds for experimental validation requires filtering these molecules based on favourable druglike properties, such as Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET). We developed ADMET-AI, a machine learning platform that provides fast and accurate ADMET predictions both as a website and as a Python package. ADMET-AI has the highest average rank on the TDC ADMET Benchmark Group leaderboard, and it is currently the fastest web-based ADMET predictor, with a 45% reduction in time compared to the next fastest ADMET web server. ADMET-AI can also be run locally with predictions for one million molecules taking just 3.1 hours.Availability and ImplementationThe ADMET-AI platform is freely available both as a web server atadmet.ai.greenstonebio.comand as an open-source Python package for local batch prediction atgithub.com/swansonk14/admet_ai(also archived on Zenodo atdoi.org/10.5281/zenodo.10372930). All data and models are archived on Zenodo atdoi.org/10.5281/zenodo.10372418.