bluuebunny/crossref_metadata_2025_split huggingface dataset:
Input / Output Relationships for the Primary Hippocampal Circuit
Authors: Gunn BG , Pruess BS , Gall CM , Lynch G 
Published: November 2023

AbstractThe hippocampus is likely the most studied brain region but little is known about signal throughput –– the simplest, yet most essential of circuit operations –– across its multiple stages from perforant path input to CA1. Here we report that single pulse stimulation of the lateral perforant path (LPP) produces a two-part CA1 response generated by projections to CA3 („direct path‟) and the dentate gyrus („indirect path‟). The latter was by far the more potent in driving CA1 output because it engaged the massive recurrent collateral system and elicited a series of fEPSPs and spikes in CA3. The mobilization time for this stereotyped sharp wave-like response resulted in surprisingly slow throughput. The circuit did not convey high frequency LPP trains but transmitted single pulses, or bursts of pulses separated by the period of the theta wave. During these activation patterns CA1 output faithfully reproduced a version of the LPP input. We conclude that the basic hippocampal circuit, despite its considerable complexity, has a default mode in which select cortical signals are reliably transferred to output stations.Significance statementThe hippocampus, a brain structure synonymous with episodic memory, is one of the most studied brain regions in neuroscience today. However, despite this intense interest, surprisingly little is known about how signals are transformed and processed by the hippocampal circuit. As a result, there are currently no “bottom up” hypotheses about how the structure supports its physiological function(s). Here, we use a novel brain slice preparation to describe the signal transformations occurring across the primary hippocampal circuit. The results identify novel circuit operations that challenge the notion of the tri-synaptic circuit and provide evidence for frequency-dependent filters that are critical for determining signal throughput. These findings provide an initial link between basic circuit function(s) and events recorded in behaving animals.
VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction
Authors: Blankenship Harris E. , Carter Kelsey A. , Cassidy Nina T. , Markiewicz Andrea N. , Thellmann Michael I. , Sharpe Amanda L. , Freeman Willard M. , Beckstead Michael J. 
Published: November 2023

ABSTRACTAlzheimer’s disease (AD) patients exhibit neuropsychiatric symptoms that extend beyond classical cognitive deficits, suggesting involvement of subcortical areas. Here, we investigated the role of midbrain dopamine (DA) neurons in AD using the amyloid + tau-driven 3xTg-AD mouse model. We found deficits in reward-based operant learning in AD mice, suggesting possible VTA DA neuron dysregulation. Physiological assessment revealed hyperexcitability and disrupted firing in DA neurons caused by reduced activity of small-conductance calcium-activated potassium (SK) channels. RNA sequencing from contents of single patch-clamped DA neurons (Patch-seq) identified up-regulation of the SK channel modulator casein kinase 2 (CK2). Pharmacological inhibition of CK2 restored SK channel activity and normal firing patterns in 3xTg-AD mice. These findings shed light on a complex interplay between neuropsychiatric symptoms and subcortical circuits in AD, paving the way for novel treatment strategies.
Massively parallel quantification of substrate turnover defines protease subsite cooperativity
Authors: Gudipati Rajani Kanth , Gaidatzis Dimos , Seebacher Jan , Muehlhaeusser Sandra , Kempf Georg , Cavadini Simone , Hess Daniel , Soneson Charlotte , Großhans Helge 
Published: November 2023

AbstractSubstrate specificity determines protease functions in physiology and in clinical and biotechnological application, yet quantitative cleavage information is often unavailable, biased, or limited to a small number of events. Here, we develop qPISA (quantitative Protease specificity Inference from Substrate Analysis) to studyDipeptidylPeptidase Four (DPP4), a key regulator of blood glucose levels. We use mass spectrometry to quantify its effects on >40,000 peptides from a complex, commercially available peptide mixture. By determining substrate turnover instead of focusing on product identification, we can reveal cooperative interactions within DPP4’s active pocket and derive a sequence motif that predicts activity quantitatively. qPISA distinguishes DPP4 from the relatedC. elegansDPF-3 (a DPP8/9 orthologue), and we relate the differences to structural features of the two enzymes. We demonstrate that qPISA can direct protein engineering efforts like stabilization of GLP-1, a key DPP4 substrate used in treatment of diabetes and obesity. Thus, qPISA offers a versatile approach for profiling protease and especially exopeptidase specificity, facilitating insight into enzyme mechanisms and biotechnological and clinical applications.
NeuroVelo: interpretable learning of temporal cellular dynamics from single-cell data
Authors: Kouadri Boudjelthia Idris , Milite Salvatore , El Kazwini Nour , Huang Yuanhua , Sottoriva Andrea , Sanguinetti Guido 
Published: November 2023

AbstractReconstructing temporal cellular dynamics from static single-cell transcriptomics remains a major challenge. Methods based on RNA velocity are useful, but interpreting their results to learn new biology remains difficult, and their predictive power is limited. Here we propose NeuroVelo, a method that couples learning of an optimal linear projection with non-linear Neural Ordinary Differential Equations. Unlike current methods, it uses dynamical systems theory to model biological processes over time, hence NeuroVelo can identify what genes and mechanisms drive the temporal cellular dynamics. We benchmark NeuroVelo against several state-of-the-art methods using single-cell datasets, demonstrating that NeuroVelo has high predictive power but is superior to competing methods in identifying the mechanisms that drive cellular dynamics over time. We also show how we can use this method to infer gene regulatory networks that drive cell fate directly from the data.
An Open-Access Database of Video Stimuli for Action Observation Research in Neuroimaging Settings: Psychometric Evaluation and Motion Characterization
Authors: Georgiev Christian , Legrand Thomas , Mongold Scott J. , Fiedler-Valenta Manoa , Guittard Frédéric , Bourguignon Mathieu 
Published: November 2023

AbstractVideo presentation has become ubiquitous in paradigms investigating the neural and behavioral responses to observed actions. In spite of the great interest in uncovering the processing of observed bodily movements and actions in neuroscience and cognitive science, at present, no standardized set of video stimuli for action observation research in neuroimaging settings exists. To facilitate future action observation research, we developed an open-access database of 135 high-definition videos of a male actor performing object-oriented actions. Actions from 3 categories: kinematically natural and goal-intact (Normal), kinematically unnatural and goal-intact (How), or kinematically natural and goal-violating (What), directed towards 15 different objects were filmed from 3 angles. Psychometric evaluation of the database revealed high video recognition accuracy (Meanaccuracy = 88.61 %) and substantial inter-rater agreement (Fleiss’Kappa= 0.702), establishing excellent validity and reliability. Videos’ exact timing of motion onset was identified using a custom motion detection frame-differencing procedure. Based on its outcome, the videos were edited to assure that motion begins at the second frame of each video. The videos’ timing of category recognition was also identified using a novel behavioral up-down staircase procedure. The identified timings can be incorporated in future experimental designs to counteract jittered stimulus onsets, thus vastly improving the sensitivity of neuroimaging experiments. All videos, their psychometric evaluations, and the timing of their frame of category recognition, as well as our custom programs for performing these evaluations on our, or on other similar video databases, are available at the Open Science Framework (https://osf.io/zexc4/).
DeepLocRNA: An Interpretable Deep Learning Model for Predicting RNA Subcellular Localization with domain-specific transfer-learning
Authors: Wang Jun , Horlacher Marc , Cheng Lixin , Winther Ole 
Published: November 2023

ABSTRACTAccurate prediction of RNA subcellular localization plays an important role in understanding cellular processes and functions. Although post-transcriptional processes are governed by trans-acting RNA-binding proteins (RBPs) through interaction with cis-regulatory RNA motifs, current methods do not incorporate RBP-binding information. In this paper, we propose DeepLocRNA, an interpretable deep-learning model that leverages a pre-trained multi-task RBP-binding prediction model to predict the subcellular localisation of RNA molecules via fine-tuning. We constructed DeepLocRNA using a comprehensive dataset with variant RNA types and evaluated it on held-out RNA species. Our model achieved state-of-the-art performance in predicting RNA subcellular localization in mRNA and miRNA. It has demonstrated great generalization capabilities, not only for human RNA but also for mice. Moreover, the interpretability of the model is enhanced through the motif analysis, enabling the understanding of the signal factors that contribute to the predictions. The proposed model provides general and powerful prediction abilities for different RNA and species, offering valuable insights into the localisation patterns of RNA molecules and contributing to advancing our understanding of cellular processes at the molecular level.
A chromosome-level genome assembly ofSolanum chilense, a tomato wild relative associated with resistance to salinity and drought
Authors: Molitor Corentin , Kurowski Tomasz J. , Fidalgo de Almeida Pedro M , Kevei Zoltan , Spindlow Daniel J. , Chacko Kaitholil Steffimol R. , Iheanyichi Justice U. , Prasanna HC , Thompson Andrew J. , Mohareb Fady R. 
Published: November 2023

AbstractSolanum chilenseis a wild relative of tomato reported to exhibit resistance to biotic and abiotic stresses. There is potential to improve tomato cultivars via breeding with wild relatives, a process greatly accelerated by suitable genomic and genetic resources. In this study we generated a high-quality, chromosome-level,de novoassembly for theS. chilenseaccession LA1972 using a hybrid assembly strategy with ∼180 Gbp of Illumina short reads and ∼50 Gbp long PacBio reads. Further scaffolding was performed using Bionano optical maps and 10x Chromium® reads. The resulting sequences were arranged into 12 pseudomolecules using Hi-C sequencing. This resulted in a 901 Mbp assembly, with a completeness of 95%, as determined by Benchmarking with Universal Single-Copy Orthologs (BUSCO). Sequencing of RNA from multiple tissues resulting in ∼219 Gbp of reads was used to annotate the genome assembly with an RNA-Seq guided gene prediction, and for ade novotranscriptome assembly. This chromosome-level, high-quality reference genome forS. chilenseaccession LA1972 will support future breeding efforts for more sustainable tomato production. Gene sequences related to drought and salt resistance were compared betweenS. chilenseandS. lycopersicumto identify amino acid variations with high potential for functional impact. These variants were subsequently analysed in 84 resequenced tomato lines across 12 different related species to explore the variant distributions. We identified a set of 7 putative impactful amino acid variants some of which may also impact on fruit development for example the ethylene-responsive transcription factor WIN1andethylene-insensitive protein 2. These variants could be tested for their ability to confer functional phenotypes to cultivars that have lost these variants.
Reversible histone deacetylase activity catalyzes lysine acylation
Authors: Tsusaka Takeshi , Najar Mohd. Altaf , Schwarz Benjamin , Bohrnsen Eric , Oses-Prieto Juan A. , Lee Christina , Burlingame Alma L. , Bosio Catharine M. , Burslem George M. , Goldberg Emily L. 
Published: November 2023

AbstractStarvation and low carbohydrate diets lead to the accumulation of the ketone body, β-hydroxybutyrate (BHB), whose blood concentrations increase more than 10-fold into the millimolar range. In addition to providing a carbon source, BHB accumulation triggers lysine β-hydroxybutyrylation (Kbhb) of proteins via unknown mechanisms. As with other lysine acylation events, Kbhb marks can be removed by histone deacetylases (HDACs). Here, we report that class I HDACs unexpectedly catalyze protein lysine modification with β-hydroxybutyrate (BHB). Mutational analyses of the HDAC2 active site reveal a shared reliance on key amino acids for classical deacetylation and non-canonical HDAC-catalyzed β-hydroxybutyrylation. Also consistent with reverse HDAC activity, Kbhb formation is driven by mass action and substrate availability. This reverse HDAC activity is not limited to BHB but also extends to multiple short-chain fatty acids. The reversible activity of class I HDACs described here represents a novel mechanism of PTM deposition relevant to metabolically-sensitive proteome modifications.
Pseudomonas syringaepv.tomatoDC3000 induces defense responses in diverse maize inbred lines
Authors: Jaiswal Namrata , Helm Matthew 
Published: November 2023

ABSTRACTMany phytopathogens translocate virulence (effector) proteins into plant cells to circumvent host immune responses during infection. One such pathogen isPseudomonas syringaepv.tomatoDC3000, which secretes at least twenty-nine effectors into host cells, of which a subset elicits host defense responses in crop plant species. However, it is unknown whetherP. syringaepv.tomatoDC3000 activates immune responses in diverse maize inbreds. Here, we screened a diverse maize germplasm collection for effector-dependent recognition of this bacterial pathogen. As a control, we infiltratedPseudomonas syringaeDC3000(D36E), a derivative ofP. syringaepv.tomatoDC3000 that lacks all endogenous effectors. In our evaluations, we observed a variety of responses toP. syringaepv.tomatoDC3000 in maize and scored the phenotypes as either no observable response (N) or as one of three responses: weak chlorosis (WC), chlorosis (C) with minimal cell death, and hypersensitive reaction (HR)-like cell death. Of the twenty-six maize inbreds screened, 13 were scored as N, 2 as WC, 2 as C, and 9 as HR-like cell death. Importantly, no maize line responded toP. syringaeDC3000(D36E), demonstrating the responses observed are likely dependent upon recognition of one or morePseudomonaseffectors. Importantly, maize inbreds that recognizeP. syringaepv.tomatoDC3000 accumulated detectable hydrogen peroxide as well as an increase in transcript expression of a subset of maize defense genes. Collectively, our results will likely stimulate new research aimed at identifying the cognate maize disease resistance proteins that recognize the activities of one or more bacterial effectors.
Development of governance for an integrated public data (GIPD) framework: illustrative use of GIPD in South Korea
Authors: Kim Haengmi , An Jaeyoung , Lee Choong C. 
Published: November 2023

PurposeUpon the realization of the need for guideline in cross-organizational data integration, in an exploratory manner, this study developed a public data governance framework, specifically, the governance for integrated public data (GIPD) framework and identified the influential factors of its successful implementation. This framework was then subjected to an analysis of a real data integration case in the South Korean public sector to test its efficacy.Design/methodology/approachTo develop the GIPD framework, the authors conducted an extensive meta study, focus group interviews and the analytic hierarchy process involving field experts. Further, the authors performed topic modeling on documents from Korean research and development data integration projects, and compared the extracted factors to those of the GIPD to illustrate the latter's usefulness in a real case.FindingsLegislation, policy goals and strategies, operation organization, decision-making council, financial support size and objective, system development and operation, data integration, data generation, system/data standardization and master data management were derived as the 10 important factors in implementing the GIPD framework. The illustrative case of Korea revealed that decision-making council, financial support size and objective, legislation, data generation and data integration were insufficient.Research limitations/implicationsAlthough this study reveals important findings, it has a few limitations. First, the potential factors for data governance might vary depending on the attribute of the “interviewee” (such as their career or experience period) and the goal and area of GIPD framework building. Second, the inherent limitation of topic modeling in determining topics from groups of extracted keywords means that topics may be interpreted in various ways, depending on the perspective of the expert.Practical implicationsThis study is highly significant in that it provides a starting point for discussions on the issue of data integration among public institutions. Therefore, although this study examined public data governance based on R&D data, it will contribute to providing a sufficient guideline for any type of inter-institutional data governance framework, what to discuss and how to discuss between institutions.Originality/valueThe findings are expected to provide a roadmap to formulate practical guidelines on inter-institutional data cooperation and a diagnostic matrix to improve the existing data governance system, especially in the public sector, from the existing practice of empirical analysis using a mixed methodology approach.
This is not an exit: accounting education and attempting to escape the capitalist realist “cage”
Authors: Yates David , Al Mahameed Muhammad 
Published: November 2023

Purpose
Through this reflexive, theoretically informed polemical piece, this paper aims to seek to reflect on the role of accounting education in United Kingdom Higher Education (UKHE). The authors reignite an old, but pertinent debate, whether accounting graduates should be educated to be accountants or receive a holistic, critical education.

Design/methodology/approach
The authors adopt a theoretical position drawing on the work of Slavoj Žižek and Mark Fisher, and their fusion of Lacanian psychoanalysis and Marxism, in particular Fisher’s (2009) conceptualisation of “capitalist realism” to take a critical standpoint on the effects that UKHE marketisation is having on the teaching of accounting and other business-related disciplines.

Findings
The authors outline four key aspects of where accounting education in UKHE is influenced by capitalist realism, as a result of the marketisation of UKHE.

Research limitations/implications
The paper is a reflexive polemic and so is limited by this written style and presentation.

Social implications
The authors argue that capitalist realism is a dominant theme that influences accounting education. They propose that universities now, more than ever, must focus on their societal duty to foster critical viewpoints in their graduates and dispose of a model that is subject to capitalist realism ontology.

Originality/value
The theoretical stance allows for a potentially deeper consideration of issues surrounding marketisation of higher education, from the micro level of social interaction (that of the accounting academic and their impact/perceptions of the reality).
A resource-efficient form-finding approach to tensegrity structures
Authors: Liu Heping , Sanaullah  , Vumiliya Angelo , Luo Ani 
Published: November 2023

PurposeThe aim of this article is to obtain a stable tensegrity structure by using the minimum knowledge of the structure.Design/methodology/approachThree methods have been formulated based on the eigen value decomposition (EVD) and singular value decomposition theorems. These two theorems are being implemented on the matrices, which are computed from the minimal data of the structure. The required minimum data for the structure is the dimension of the structure, the connectivity matrix of the structure and the initial force density matrix computed from the type of elements. The stability of the structure is analyzed based on the rank deficiency of the force density matrix and equilibrium matrix.FindingsThe main purpose of this article is to use the defined methods to find (1) the nodal coordinates of the structure, (2) the final force density values of the structure, (3) single self-stress from multiple self-stresses and (4) the stable structure.Originality/valueBy using the defined approaches, one can understand the difference of each method, which includes, (1) the selection of eigenvalues, (2) the selection of nodal coordinates from the first decomposition theorem, (3) the selection of mechanism mode and force density values further and (4) the solution of single feasible self-stress from multiple self-stresses.
Advocating for a more active role for the user in LIS participatory research: a scoping literature review
Authors: Nesset Valerie , Vanderschantz Nicholas , Stewart-Robertson Owen , Davis Elisabeth C. 
Published: November 2023

PurposeThrough a review of the literature, this article seeks to outline and understand the evolution and extent of user–participant involvement in the existing library and information science (LIS) research to identify gaps and existing research approaches that might inform further methodological development in participant-oriented and design-based LIS research.Design/methodology/approachA scoping literature review of LIS research, from the 1960s onward, was conducted, assessing the themes and trends in understanding the user/participant within the LIS field. It traces LIS research from its early focus on information and relevancy to the “user turn”, to the rise of participatory research, especially design-based, as well as the recent inclusion of Indigenous and decolonial methodologies.FindingsThe literature review indicates that despite the reported “user turn”, LIS research often does not include the user as an active and equal participant within research projects.Originality/valueThe findings from this review support the development of alternative design research methodologies in LIS that fully include and involve research participants as full partners – from planning through dissemination of results – and suggests avenues for continuing the development of such design-based research. To that end, it lays the foundations for the introduction of a novel methodology, Action Partnership Research Design (APRD).