bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling phonology from phonological short-term memory in Alzheimer’s disease phenotypes
Authors: Henderson Shalom K. , Halai Ajay , Tsvetanov Kamen A. , Cope Thomas E. , Patterson Karalyn E. , Rowe James B. , Lambon Ralph Matthew A. 
Published: January 2025

AbstractImpaired phonological short-term memory is a core feature of the logopenic variant of primary progressive aphasia (lvPPA), but it is not clear whether a core phonological processing deficit is also present. We asked three questions: (i) beyond short-term memory impairment, do people with lvPPA have an impairment within phonology itself?; (ii) is their performance in working memory and confrontation naming reflective of this phonological impairment and/or other key contributing deficits (e.g., semantic)?; and (iii) is their repetition performance related to structural and functional differences in key language-dominant regions? We compared non- word and word repetition and short-term memory performance in patients with typical, amnestic Alzheimer’s disease (tAD,n= 9), lvPPA per consensus criteria (n= 10), and others who previously satisfied definitions of lvPPA but had progressed with multi-domain cognitive impairments (lvPPA+,n= 8). Bayesian analyses revealed no group differences in phonological tasks of word and non-word repetition. There was, however, a very strong group effect on multi-syllabic word/phrase repetition. We found very strong evidence for an effect of self- reported hearing loss on both word and non-word repetition, but not multi-syllabic word/phrase repetition. A comparison of phonological (as indexed by non-word repetition)versusworking memory (as measured by multisyllabic word repetition and digit span) and confrontation naming tasks produced either no evidence or evidence for no correlation. Confrontation naming correlated positively with multisyllabic word/phrase repetition and semantic assessments across the whole group. Beyond the expected grey matter reductions in patients relative to controls in the left posterior superior temporal gyrus, anterior temporal lobe, and inferior temporal gyrus, we found no evidence for the associations between non-word repetition and functional connectivity between all regions of interest in the whole group. When excluding controls, the only anecdotal evidence that was corroborated by frequentist multiple regression was for an association between non-word repetition and functional connectivity between dorsal premotor and posterior superior temporal gyrus after controlling for the grey matter volumes in these regions. We have shown that deficits in “pure” phonological tasks, namely single word and non-word repetition, are (i) not dependent on working memory and (ii) greater in patients with a self-reported hearing loss across all groups with lvPPA or tAD. Our results suggest that instead of having a core phonological impairment, lvPPA patients have a working memory/buffering impairment that adversely affects their performance on length-dependent working memory tasks.
A tightly regulated auxin signaling landscape is required for spatial accommodation of lateral roots inArabidopsis
Authors: Bùi Thái X. , Shekhar Vinay , Marc-Martin Sophie , Bellande Kevin , Vermeer Joop E.M. 
Published: January 2025

ABSTRACTInArabidopsis thaliana, lateral root (LR) development requires spatial accommodation responses in overlying endodermal cells. This includes loss of cell volume whilst maintaining membrane integrity to allow the expansion of the underlying LR primordia (LRPs). These accommodation responses are regulated by auxin-mediated signaling, specifically through Aux/IAA proteins, involvingIAA3/SHY2. Plants that express a stabilized version of SHY2, shy2-2, in differentiated endodermal cells,CASP1pro::shy2-2plants, fail to make LRs. Exogenous treatment with 1- naphthaleneacetic acid (NAA) was reported to partially restore LR formation in this spatial accommodation mutant. Using treatments with auxins with different transport properties, such as NAA, indole-3-acetic acid (IAA), and 2,4-dichlorophenoxyacetic acid (2,4-D), we assessed the ability of each auxin to rescue LR formation inCASP1pro::shy2-2roots. This revealed that IAA is the most effective in partially restoring LR development, NAA is effective in inducing LRPs but cannot maintain their canonical phenotype, whereas 2,4-D induces non-controlled cell divisions. In addition, we show that inCASP1pro::shy2-2 roots,AUX1appears to be repressed in the zone where oscillation of the auxin response have been described. Our study advances the understanding of auxin-regulated spatial accommodation mechanisms during LRP formation and highlights the complex interplay of auxin transport and signaling in bypassing the endodermal constraints.
Ancient gene clusters initiate monoterpenoid indole alkaloid biosynthesis and C3 stereochemistry inversion
Authors: Hwang Jaewook , Kirshner Jonathan , Ramey Deschênes Daniel André , Richardson Matthew Bailey , Fleck Steven J. , Guo Jun , Perley Jacob Owen , Shahsavarani Mohammadamin , Garza-Garcia Jorge Jonathan Oswaldo , Seveck Alyssa Dawn , Doiron Savannah Sadie , Mai Zhan , Silliphant Stephen Nelson , Calhoun Larry , Gao Di , Lian Jiazhang , Deslongchamps Ghislain , Albert Victor A. , Qu Yang 
Published: January 2025

AbstractThe inversion of C3 stereochemistry in monoterpenoid indole alkaloids (MIAs), derived from the central precursor strictosidine (3S), is essential for synthesizing numerous 3RMIAs and oxindoles, including the antihypertensive drug reserpine found inRauvolfia serpentina(Indian snakeroot) andRauvolfia tetraphylla(devil pepper) of the plant family Apocynaceae. MIA biosynthesis begins with the reduction of strictosidine aglycone by various reductases, preserving the initial 3Sstereochemistry. In this study, we identify and biochemically characterize a conserved oxidase-reductase pair from the Apocynaceae, Rubiaceae, and Gelsemiaceae families of the order Gentianales: the heteroyohimbine/yohimbine/corynanthe C3-oxidase (HYC3O) and C3-reductase (HYC3R). These enzymes collaboratively invert the 3Sstereochemistry to 3Racross a range of substrates, resolving the long-standing question about the origin of 3RMIAs and oxindole derivatives, and facilitation of reserpine biosynthesis. Notably,HYC3OandHYC3Rare located within gene clusters in both theR. tetraphyllaandCatharanthus roseus(Madagascar periwinkle) genomes, which are partially homologous to an elusive geissoschizine synthase (GS) gene cluster we also identified in these species. InR. tetraphylla, these clusters occur closely in tandem on a single chromosome, likely stemming from a single segmental duplication event, while inC. roseus, a closely related member of rauvolfioid Apocynaceae, they were later separated by a chromosomal translocation. The ancestral genomic context for both clusters can be traced all the way back to common ancestry with grapevine. Given the presence of syntenic GS homologs inMitragyna speciosa(Rubiaceae), the GS cluster, at least in part, probably evolved at the base of the Gentianales, which split from other core eudicots up to 135 million years ago. We also show that the strictosidine biosynthetic gene cluster, required to initiate the MIA pathway, plausibly evolved concurrently. The reserpine biosynthetic cluster likely arose much later in the rauvolfioid lineage of Apocynaceae. Collectively, our work uncovers the genomic and biochemical basis for key events in MIA evolution and diversification, providing insights beyond the well-characterized vinblastine and ajmaline biosynthetic pathways.
Star-Shaped Glatiramer Acetate Mitigates Pulmonary Dysfunction and Brain Neurodegeneration in a Murine Model of Cryptococcus-Associated IRIS
Authors: Anwar Shehata , Zhou Jinyan , Kowalski Lauren , Saylor Joshua , Shukla Devanshi , Boetel Katelyn , Song Ziyuan , Sharma Kamal , Cheng Jianjun , Inoue Makoto 
Published: January 2025

AbstractCryptococcal-associated immune reconstitution inflammatory syndrome (C-IRIS) is a clinical worsening or new presentation of cryptococcal disease following the initiation of antiretroviral therapy. C-IRIS is primarily driven by an influx of pathological CD4+T cells, which triggers a hyperinflammatory response. The murine model of C-IRIS is a way to study the disease in mice and understand how the immune system triggers life-threatening outcomes in patients. We previously developed a murine C-IRIS model and demonstrated that C-IRIS is triggered by pathological CD4+T cells, particularly Th1 cells, in the brain, which triggers neurodegeneration and pulmonary dysfunction. Using this unique mouse model, we tested the therapeutic effect of a star-shaped glatiramer acetate (sGA), which is a more effective isomeric form than linear GA. Here, we observed that sGA suppresses Th1 differentiation in the lung tissues, reducing CD4+T cell and Th1 cell count. It also reduced microglia populations in the brain. Together, these changes improved respiratory dysfunction caused by C-IRIS, lowered mortality rate, and reduced brain neurodegeneration. These findings suggest that sGA could be an effective therapeutic strategy for managing C-IRIS.
Variance spectrum scaling analysis for high-dimensional coordination in human movement
Authors: Dotov Dobromir , Gu Jingxian , Hotor Philip , Spyra Joanna 
Published: January 2025

AbstractCoordinated movement has been essential to our evolution as a species but its study has been limited by ideas largely developed for one-dimensional data. The field is poised for a change by high-density recording tools and the popularity of data sharing. New ideas are needed to revive classical theoretical questions such as the organization of the highly redundant biomechanical degrees of freedom and the optimal distribution of variability for efficiency and adaptiveness. Methods have been focused on increasing dimensions: making inferences from one or few measured dimensions about the properties of a higher dimensional system. The opposite problem is to record 100+ kinematic degrees of freedom and make inferences about properties of the embedded manifold. We present an approach to quantify the smoothness and degree to which the manifold is distributed among embedding dimensions. The principal components of embedding dimensions are rank-ordered by variance. The power-law scaling exponent of this variance spectrum is a function of the smoothness and dimensionality of the embedded manifold. It defines a threshold value beyond which the manifold becomes non-differentiable. We verified this approach by showing that the Kuramoto model close to global synchronization in the upper critical end of the coupling parameter obeys the threshold. Next, we tested if the scaling exponent was sensitive to participants’ gait impairment in a full-body motion capture dataset containing short gait trials. Variance scaling was highest in the healthy individuals, followed by osteoarthritis patients after hip-replacement, and lastly, the same patients pre-surgery. Thinking about manifold dimensionality, smoothness, and scaling could inform classic problems in movement science and exploration of the biomechanics of full-body action.
Descriptron: Testing Artificial Intelligence for Automating Taxonomic Species Descriptions with a User-friendly Software Package
Authors: Van Dam Alex R. , Serbina Liliya Štarhová 
Published: January 2025

AbstractRecent advances in Computer Vision, Convolutional Neural Networks (CNNs), Vision Transformers (ViTs) and Large Language Models (LLMs) suggest that it may be possible to approach mimicking the ability to decode knowledge about morphology and taxonomy to describe species in an automated way. Here we test for the first time a current state-of-the-art Vision Language Model (VLM) to approximate taxonomic species descriptions in an automated manner. The test utilizes a new graphical user interface,Descriptron, that collects data about biological images and transmits this highly specialized knowledge to a VLM to decode the taxonomic knowledge encoded in labeled biological images with text. Our results indicate that current state-of-the-art VLM (GPT-4o) can produce automated species descriptions that with error correction approximate taxonomists’ ability to describe morphological features of species and organize them in taxonomic keys. However, the results are not without significant errors and the VLM requires the input of the taxonomists knowledge to prevent widespread hallucinations by the VLM. We find here that the taxonomist is clearly needed to both teach and closely supervise the VLM. However, the time saved by utilizingDescriptronis also significant. Taxonomists remain essential for teaching and closely supervising the VLM. The time saved by utilizingDescriptronare nevertheless already very significant. TheDescriptronprogram and supporting example prompt files are free to use under an Apache2 License available from:https://github.com/alexrvandam/Descriptron.
Conformation-gated binding drives negative cooperativity in ATP:cob(I)alamin Adenosyltransferase for optimized cobalamin handling
Authors: Yan Guangjie , Pan Manhua , Keller Aaron M. , Santiago Ace George , Lofgren Michael , Banerjee Ruma , Chen Peng , Chen Tai-Yen 
Published: January 2025

AbstractVitamin B12(cobalamin) is a high-value yet scarce cofactor required for various metabolic processes, making its efficient handling important for maintaining metabolic homeostasis. While the involvement of ATP:cob(I)alamin adenosyltransferases (MMAB) in the synthesis, delivery, and repair of 5’-deoxyadenosylcobalamin (AdoCbl) is well established, the kinetic mechanisms that regulate this process, particularly its negative cooperativity, remain poorly understood. Understanding these mechanisms is key to clarifying how MMAB efficiently uses AdoCbl, prevents resource wastage, and supports bacterial survival in nutrient-limited environments. Using single-molecule relative fluorescence (SRF) spectroscopy, we found that conformation-gated binding is the driving force behind MMAB’s preference for AdoCbl over hydroxocobalamin and is the underlying mechanism for negative cooperativity. This mechanism significantly slows down the binding of the second equivalent of AdoCbl, favoring the singly bound state. Our findings indicate that MMAB predominantly binds a single AdoCbl, optimizing the AdoCbl loading to methylmalonyl-CoA mutase. Additionally, our SRF approach also serves as a tool to explore other cofactor interactions, such as those between riboswitches and cobalamin derivatives, to provide insights into regulatory mechanisms of cobalamin sensing and gene regulation, which are crucial for bacterial adaptation to changing nutrient conditions.Significance StatementMMAB is important for B12-dependent propionate metabolism in bacteria. Our findings reveal that conformation-driven binding mechanism underlines the negative cooperativity of MMAB, as it favors the binding of the first AdoCbl while limiting further binding. The largerkonfor the first site, combined with similar unbinding rates for both sites, could provide a solution for optimizing cobalamin handling and minimize unnecessary waste. Our single-molecule fluorescence approach offers a powerful tool for investigating other dynamic cofactor interactions, providing new insights into regulatory mechanisms in bacterial metabolism.
Backbone and Sidechain1H,15N and13C Resonance Assignments of a Multidrug Efflux Membrane Protein using Solution and Solid-State NMR
Authors: Harding Benjamin D. , Hiett Ashley , Tonelli Marco , Wang Songlin , Rienstra Chad M. , Henzler-Wildman Katherine A. 
Published: January 2025

AbstractEmrE is a bacterial membrane-embedded multidrug transporter that functions as an asymmetric homodimer. EmrE is implicated in antibiotic resistance, but is now known to confer either resistance or susceptibility depending on the identity of the small molecule substrate. Here, we report both solution- and solid-state NMR assignments of S64V-EmrE at pH 5.8, below the pKa of critical residues E14 and H110. This includes1H,15N, and13C resonance assignments of the backbone, methyl groups (isoleucine, leucine, valine, threonine and alanine) from solution NMR experiments in bicelles, and backbone and side-chain assignments from solid-state NMR13C-detected experiments in liposomes.
Ustilaginoidea virenssuppresses floral immunity through promoting GA biosynthesis by the effector SCRE9
Authors: Yu Siwen , Zhang Shaoqi , Zheng Xinhang , Li Xiaoai , Wang Jiyang , Duan Guohua , Qiu Shanshan , Zhao Dan , Nan Nan , Yu Qianheng , Jiang Chunquan , Peng Zhao , Li Dayong , Sun Wenxian 
Published: January 2025

AbstractRice false smut caused byUstilaginoidea virenshas become one of the most important rice diseases.U. virensspecifically infects rice florets through stamen filaments. However, it is mysterious howU. virensinhibits floral immunity for successful colonization. Here, we show that a small cysteine-rich effector SCRE9 is a key virulence factor inU. virens. Expression of SCRE9 in rice not only suppresses immune responses and false smut resistance, but also significantly increases expression of expansin and gibberellin (GA) biosynthetic genes and GA content in young rice panicles. We further demonstrate that OsSIP1 (SCRE9-interacting protein 1) in rice is targeted by SCRE9 and interacts with the OsMADS63 and OsMADS68 transcription factors that transcriptionally regulate the GA synthesis geneGA3ox1. Interestingly, the chloroplast-localized OsSIP1 recruits OsMADS63/68 into the chloroplast. SCRE9 causes OsSIP1 to be translocated into the nucleus, thereby releasing OsMADS63/68 from the chloroplast into the nucleus to promoteGA3ox1transcription. Therefore, SCRE9 promotes GA biosynthesis and expression of expansins in rice florets, thus loosening cell walls and overcoming the physical barrier duringU. virensinfection. The finding uncovers an unidentified floret infection strategy that offsets the deficiency in cell wall degrading ability in the unique floret colonizing fungus.
Tandem duplication of serpin genes yields functional variation and snake venom inhibitors
Authors: Ward Meilyn S. , Holding Matthew L. , Haynes Laura M. , Ginsburg David 
Published: January 2025

AbstractTandem duplication of genes can play a critical role in the evolution of functional novelty, but our understanding is limited concerning gene duplication’s role in coevolution between species. Much is known about the evolution and function of tandemly duplicated snake venom genes, however the potential of gene duplication to fuel venom resistance within prey species is poorly understood. In this study, we characterize patterns of gene duplication of the SERPINA subfamily of genes across in vertebrates and experimentally characterize functional variation in the SERPINA3-like paralogs of a wild rodent. We find the hallmarks of rapid birth-death evolution of SERPINA1-like and SERPINA3-like genes within and between rodent lineages. Next, we recombinantly expressed the 2 paralogous duplicates of SERPINA1 and 12 paralogous duplicates of SERPINA3 found in the genome of the big-eared woodrat (Neotoma macrotis), a species known to be resistant to protease-rich rattlesnake venoms. We found that two SERPINA3 paralogs inhibit snake venom serine proteases, indicating that these proteins have potential as resistance factors in SERPIN-mediated venom resistance. In addition, functional variation is apparent among paralogs, including neofunctionalization to inhibit both chymotrypsin-like and and trypsin-like proteases simultaneously for one venom-inhibiting paralog. Our results provide further evidence that the rapid evolution of SERPINA1 and SERPINA3 gene copy number across rodents has adaptive potential by producing functionally-diverse inhibitors.
An intranasal, NLC-delivered self-amplifying RNA vaccine establishes protective immunity against pre-pandemic H5N1 and H7N9 influenza
Authors: Ykema Matthew R. , Davis Michael A. , Kasal Darshan N. , Jennewein Madeleine F. , Lo Ethan , Singh Jasneet , Beaver Samuel , Cross Noah , Melief Eduard , Reed Sierra , Press Christopher , Fusco Pauline , Bakken Julie , Casper Corey , Hartwig Airn Tolnay , Gerhardt Alana , Bowen Richard A. , Voigt Emily A. 
Published: January 2025

ABSTRACTSeasonal and pandemic influenzas are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. New RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent self-amplifying RNA (saRNA) vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/2013 H7N9. These saRNA vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The saRNA-NLC vaccines provided complete protection against morbidity and mortality in ferret challenge models, establishing this intranasally-administered saRNA-NLC vaccine platform as a potential pandemic response tool.ONE SENTENCE SUMMARYA self-amplifying RNA-NLC vaccine, delivered intranasally, induces robust mucosal immunity in mice and protects against H5N1 and H7N9 in ferrets
When Stopping Requires Going; Physiological Similarities Between Action Cancellation and the Cancellation of Action Cancellation
Authors: Weber Simon , Salomoni Sauro E. , Hinder Mark R. 
Published: January 2025

AbstractThe reactive cancellation of real-world actions typically requires complex combinations of both muscle contraction and/or muscle suppression. However, current experimental paradigms solely examine contexts in which action cancellation requires muscle suppression. To provide fundamental insights into inhibitory control mechanisms, we directly compared the latency of action cancellation in novel paradigms where ‘stopping’ required either suppression of planned activation or reinstatement of ongoing activity.20 healthy adults (mean age = 32.2 years) completed novel variants of the stop signal task (SST) in which each trial began with tonic force production to depress two buttons. When a go signal appeared, participants were required to release these buttons. On a subset of trials, a stop signal occurred after a brief delay, and participants were required to cancel the release of one of the buttons. Data in these variants were compared to conventional response-selective SSTs, in which the go signal required bilateral button presses and stop signals necessitated cancellation of one of these responses. Electromyographic (EMG) recordings allowed detailed comparison of the characteristics of muscle contraction and suppression (i.e., stopping speed) across these tasks.When physiological evidence of synchronous action cancellation in both hands was observed (supporting recent models of complex stopping), EMG measures of action cancellation speed did not differ (p = 0.863, BF01 = 8.49) between cancellation of releases and cancellation of presses conditions. This result suggests that response inhibition may broadly characterise reactive control to maintain a current physiological state rather than specific cancellation of a voluntary response.