bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model-based inference of synaptic plasticity rules
Authors: Mehta Yash , Tyulmankov Danil , Rajagopalan Adithya E. , Turner Glenn C. , Fitzgerald James E. , Funke Jan 
Published: December 2023

AbstractInferring the synaptic plasticity rules that govern learning in the brain is a key challenge in neuroscience. We present a novel computational method to infer these rules from experimental data, applicable to both neural and behavioral data. Our approach approximates plasticity rules using a parameterized function, employing either truncated Taylor series for theoretical interpretability or multilayer perceptrons. These plasticity parameters are optimized via gradient descent over entire trajectories to align closely with observed neural activity or behavioral learning dynamics. This method can uncover complex rules that induce long nonlinear time dependencies, particularly involving factors like postsynaptic activity and current synaptic weights. We validate our approach through simulations, successfully recovering established rules such as Oja’s, as well as more intricate plasticity rules with reward-modulated terms. We assess the robustness of our technique to noise and apply it to behavioral data fromDrosophilain a probabilistic reward-learning experiment. Notably, our findings reveal an active forgetting component in reward learning in flies, improving predictive accuracy over previous models. This modeling framework offers a promising new avenue for elucidating the computational principles of synaptic plasticity and learning in the brain.
Limited potexvirus diversity in eastern Gulf of Mexico seagrass meadows
Authors: Lim Shen Jean , Rosario Karyna , Kernbach Meredith E. , Gross Anthony J. , Furman Bradley T. , Breitbart Mya 
Published: December 2023

2.AbstractTurtlegrass virus X, which infects the seagrassThalassia testudinum, is the only potexvirus known to infect marine flowering plants. We investigated potexvirus distribution in seagrasses using a degenerate reverse transcription polymerase chain reaction (RT-PCR) assay originally designed to capture potexvirus diversity in terrestrial plants. The assay, which implements Potex-5 and Potex-2RC primers, successfully amplified a 584 nt RNA-dependent RNA polymerase (RdRp) fragment from TVX-infected seagrasses. Following validation, we screened 74 opportunistically collected, apparently healthy seagrass samples for potexviruses using this RT-PCR assay. The survey examined the host speciesT. testudinum, Halodule wrightii, Halophila stipulacea, Syringodium filiforme, Ruppia maritima, andZostera marina. Potexvirus PCR products were successfully generated only fromT. testudinumsamples and phylogenetic analysis of sequenced PCR products revealed five distinct TVX sequence variants. Although the RT-PCR assay revealed limited potexvirus diversity in seagrasses, the expanded geographic distribution of TVX shown here emphasizes the importance of future studies to investigateT. testudinumpopulations across its native range and understand how the observed fine-scale genetic diversity a?ects host-virus interactions.3.Impact statementPotexviruses are widespread in terrestrial plants; however, the recent discovery of TVX in the seagrassThalassia testudinumextends their host range to marine flowering plants. Here we use existing Potex-5 and Potex-2RC degenerate primers to explore potexvirus infections in several seagrass species. TVX sequence variants were detected inT. testudinumcollected from the eastern Gulf of Mexico, uncovering previously unknown genetic diversity of this poorly understood virus.4.Data summaryAll sequence data are available in NCBI GenBank under the accession numbersOR827692-OR827705,OR854648,OR863396,OR879052-OR879056, andPP430548-PP430571. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
ER-anchored protein sorting controls the fate of two proteasome activators for intracellular organelle communication during proteotoxic stress
Authors: Langin Gautier , Raffeiner Margot , Biermann David , Franz-Wachtel Mirita , Spinti Daniela , Börnke Frederik , Macek Boris , Üstün Suayib 
Published: December 2023

SummaryProteotoxic stress, characterized by the accumulation of damaged proteins, poses a significant challenge to cellular homeostasis. To mitigate proteotoxicity eukaryotes employ the proteasome that is regulated by proteasome activators, e.g. transcription factors that promote gene expression of proteasome subunits. As proteotoxicity originates in different compartments, cells need to perceive signals from various locations. Understanding which components integrate signals to address proteotoxicity is essential to develop strategies to cope with proteotoxicity but remain elusive. Here, we identify that the proteasome autoregulatory feedback loop acts as a gatekeeper to facilitate the communication between nucleus and chloroplast. We reveal that the ER-anchored protein sorting system (ERAPS) controls the proteasomal degradation or nuclear translocation of proteasome activators NAC53 and NAC78. While both transcription factors activate the proteasome gene expression, they repress photosynthesis-associated nuclear genes during proteotoxicity through association with a conserved cis-element. Our data implicate a general trade-off between proteasome function and energy metabolism unravelling an unprecedented mechanism of how eukaryotic cells cope with proteotoxicity. Collectively, our discoveries provide a novel conceptual framework in which the proteasome autoregulatory feedback loop coordinates subcellular proteostasis and the trade-off between growth and defence.
Prediction of DNA i-Motifs Via Machine Learning
Authors: Yang Bibo , Guneri Dilek , Yu Haopeng , Wright Elisé P. , Chen Wenqian , Waller Zoë A. E. , Ding Yiliang 
Published: December 2023

ABSTRACTi-Motifs (iMs), are secondary structures formed in cytosine-rich DNA sequences and are involved in multiple functions in the genome. Although putative iM forming sequences are widely distributed in the human genome, the folding status and strength of putative iMs vary dramatically. Much previous research on iM has focused on assessing the iM folding properties using biophysical experiments. However, there are no dedicated computational tools for predicting the folding status and strength of iM structures. Here, we introduce a machine learning pipeline, iM-Seeker, to predict both folding status and structural stability of DNA iMs. The programme iM-Seeker incorporates a Balanced Random Forest classifier trained on genome-wide iMab antibody-based CUT&Tag sequencing data to predict the folding status and an Extreme Gradient Boosting regressor to estimate the folding strength according to both literature biophysical data and our in-house biophysical experiments. iM-Seeker predicts DNA iM folding status with a classification accuracy of 81% and estimates the folding strength with coefficient of determination (R2) of 0.642 on the test set. Model interpretation confirms that the nucleotide composition of the C-rich sequence significantly affects iM stability, with a positive correlation with sequences containing cytosine and thymine and a negative correlation with guanine and adenine.GRAPHICAL ABSTRACT
Transposable elements may enhance antiviral resistance in HIV-1 elite controllers
Authors: Singh Manvendra , Leddy Sabrina M. , Iñiguez Luis Pedro , Bendall Matthew L. , Nixon Douglas F. , Feschotte Cédric 
Published: December 2023

AbstractLess than 0.5% of people living with HIV-1 are elite controllers (ECs) - individuals who have a replication-competent viral reservoir in their CD4+T cells but maintain undetectable plasma viremia without the help of antiretroviral therapy. While the EC CD4+T cell transcriptome has been investigated for gene expression signatures associated with disease progression (or, in this case, a lack thereof), the expression and regulatory activity of transposable elements (TEs) in ECs has not been explored. Yet previous studies have established that TEs can directly impact the immune response to pathogens, including HIV-1. Thus, we hypothesize that the regulatory activities of TEs could contribute to the natural resistance of ECs against HIV-1. We perform a TE-centric analysis of previously published multi-omics data derived from EC individuals and other populations. We find that the CD4+T cell transcriptome and retrotranscriptome of ECs are distinct from healthy controls, treated patients, and viremic progressors. However, there is a substantial level of transcriptomic heterogeneity among ECs. We categorize individuals with distinct chromatin accessibility and expression profiles into four clusters within the EC group, each possessing unique repertoires of TEs and antiviral factors. Notably, several TE families with known immuno-regulatory activity are differentially expressed among ECs. Their transcript levels in ECs positively correlate with their chromatin accessibility and negatively correlate with the expression of their KRAB zinc-finger (KZNF) repressors. This coordinated variation is seen at the level of individual TE loci likely acting or, in some cases, known to act ascis-regulatory elements for nearby genes involved in the immune response and HIV-1 restriction. Based on these results, we propose that the EC phenotype is driven in part by the reduced availability of specific KZNF proteins to repress TE-derivedcis-regulatory elements for antiviral genes, thereby heightening their basal level of resistance to HIV-1 infection. Our study reveals considerable heterogeneity in the CD4+T cell transcriptome of ECs, including variable expression of TEs and their KZNF controllers, that must be taken into consideration to decipher the mechanisms enabling HIV-1 control.
Too much or not enough? Optimal level of human intracranial theta activity for rule-switching in the subthalamo-medio-prefrontal circuit
Authors: Laquitaine Maëva , Polosan Mircea , Kahane Philippe , Chabardes Stephan , Yelnik Jérôme , Fernandez-Vidal Sara , Domenech Philippe , Bastin Julien 
Published: December 2023

AbstractThe ability to strategically switch between rules associating stimuli and responses as a function of changing environmental demands critically depend on a neural circuit including the dorsomedial prefrontal cortex (dmPFC) and the basal ganglia. However, the precise neural implementations of rule switching remain unclear. To address this issue, we recorded local field potentials from two groups of rare patients performing a rule-switching paradigm: (1) deep brain recordings of the subthalamic nucleus (STN) in patients with obsessive-compulsive disorder, and (2) stereo-electroencephalogram from dmPFC of drug-resistant epileptic patients. We fitted a hierarchical drift-diffusion model (HDDM) to patients’ choice behavior and found that rule-switching was associated with a shift in the starting point of evidence accumulation (z), effectively disentangling rule switches from the selection of a new response. At the neural level, we found that theta band (5-10 Hz) activity increased in dmPFC and STN during switch compared to non-switch trials, while temporally delayed and excessive levels of theta activity led to premature switch errors. This seemingly opposing impact of increased theta rhythms in successful and unsuccessful switching could be explained mechanistically using a neural HDDM, as trial-by-trial fluctuations in theta power negatively correlated with the subjects’ starting point parameter. Together, these results shed a new light on the neural mechanisms underlying the rapid reconfiguration of stimulus-response associations, revealing a Goldilocks’ effect of theta band activity on rule switching behavior.
Single extracellular vesicle imaging and computational analysis identifies inherent architectural heterogeneity
Authors: Kapoor Kshipra S. , Kong Seoyun , Sugimoto Hikaru , Guo Wenhua , Boominathan Vivek , Chen Yi-Lin , Biswal Sibani Lisa , Terlier Tanguy , McAndrews Kathleen M. , Kalluri Raghu 
Published: December 2023

AbstractEvaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM) which has an inherent ability to image biological samples without harsh labeling methods and while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources such as cancer cells, normal cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by our computational pipeline. Across all 7,576 independent EVs, the average eccentricity was 0.5366, and the average equivalent diameter was 132.43 nm. The architectural heterogeneity was consistent across all sources of EVs, independent of purification techniques, and compromised of single spherical (S. Spherical), rod-like or tubular, and double shapes. This study will serve as a reference foundation for high-resolution EV images and offer insights into their potential biological impact.
Gain of chromosome region 1q31.3 in human iPSCs confers growth advantage and alters contraction in derivative cardiomyocytes
Authors: Brandão Karina O. , Meraviglia Viviana , Salvatori Daniela , Cao Xu , Sala Luca , Yiangou Loukia , Mol Mervyn P.H. , Bellin Milena , Mummery Christine L. , Davis Richard P. 
Published: December 2023

SUMMARYhPSCs can acquire chromosomal aberrations such as copy number variations during prolonged maintenancein vitro, conferring growth advantages. However, the effect of these culture-acquired mutations on the phenotypes of the differentiated hPSCs is largely unstudied. Here, we identified mosaicism in a hPSC line in which some cells showed a gain of chromosome 1q31.3. We subcloned the wild-type and variant hPSCs and could maintain both as stable lines. While both variant and wildtype lines differentiated efficiently to cardiomyocytes (hPSC-CMs), molecular analysis revealed the variant hPSC-CMs had increased expression ofTNNT2, a gene encoding one of the major sarcomere proteins mediating cardiomyocyte contractility and located within the gained chromosome 1q region. Moreover, the variant hPSC-CMs showed altered contraction kinetics. Together these results highlight the importance of careful monitoring of chromosome aberrations in hPSC lines as these could have confounding effects in various applications such as disease modelling and drug discovery.
Single molecule studies of the native hair cell mechanosensory transduction complex
Authors: Clark Sarah , Mitra Jaba , Elferich Johannes , Goehring April , Ge Jingpeng , Ha Taekjip , Gouaux Eric 
Published: December 2023

AbstractHearing and balance rely on the conversion of a mechanical stimulus into an electrical signal, a process known as mechanosensory transduction (MT). In vertebrates, this process is accomplished by an MT complex that is located in hair cells of the inner ear. While the past three decades of research have identified many subunits that are important for MT and revealed interactions between these subunits, the composition and organization of a functional complex remains unknown. The major challenge associated with studying the MT complex is its extremely low abundance in hair cells; current estimates of MT complex quantity range from 3-60 attomoles per cochlea or utricle, well below the detection limit of most biochemical assays that are used to characterize macromolecular complexes. Here we describe the optimization of two single molecule assays, single molecule pull-down (SiMPull) and single molecule array (SiMoA), to study the composition and quantity of native mouse MT complexes. We demonstrate that these assays are capable of detecting and quantifying low attomoles of the native MT subunits protocadherin-15 (PCDH15) and lipoma HMGIC fusion partner-like protein 5 (LHFPL5). Our results illuminate the stoichiometry of PCDH15- and LHFPL5-containing complexes and establish SiMPull and SiMoA as productive methods for probing the abundance, composition, and arrangement of subunits in the native MT complex.Impact StatementIn the present work, the authors develop and employ single molecule methods to detect, characterize, and quantitate attomole quantities of the hair cell mechanosensory transduction complex.
IGHMBP2 deletion suppresses translation and activates the integrated stress response
Authors: Park Jesslyn E. , Desai Hetvee , Liboy-Lugo José , Gu Sohyun , Jowhar Ziad , Xu Albert , Floor Stephen N. 
Published: December 2023

ABSTRACTIGHMBP2 is a non-essential, superfamily 1 DNA/RNA helicase that is mutated in patients with rare neuromuscular diseases SMARD1 and CMT2S. IGHMBP2 is implicated in translational and transcriptional regulation via biochemical association with ribosomal proteins, pre-rRNA processing factors, and tRNA-related species. To uncover the cellular consequences of perturbing IGHMBP2, we generated full and partial IGHMBP2 deletion K562 cell lines. Using polysome profiling and a nascent protein synthesis assay, we found that IGHMBP2 deletion modestly reduces global translation. We performed Ribo-seq and RNA-seq and identified diverse gene expression changes due to IGHMBP2 deletion, including ATF4 upregulation. With recent studies showing the ISR can contribute to tRNA metabolism-linked neuropathies, we asked whether perturbing IGHMBP2 promotes ISR activation. We generated ATF4 reporter cell lines and found IGHMBP2 knockout cells demonstrate basal, chronic ISR activation. Our work expands upon the impact of IGHMBP2 in translation and elucidates molecular mechanisms that may link mutant IGHMBP2 to severe clinical phenotypes.
Fatigue crack growth rate and propagation mechanisms of SiC particle reinforced Al alloy matrix composites
Authors: Karci Adem , Erturun Veysel , Çakir Eşref , Çam Yakup 
Published: December 2023

Purpose
This study aims to investigate the fatigue crack propagation behavior of SiC particle-reinforced 2124 Al alloy composites under constant amplitude axial loading at a stress ratio of R = 0.1. For this purpose, it is performed experiments and comparatively analyze the results by producing 5, 10, 15 Vol.% SiCp-reinforced composites and unreinforced 2124 Al alloy billets with powder metallurgy (PM) production technique.

Design/methodology/approach
With the PM production technique, SiCp-reinforced composite and unreinforced 2124 Al alloy billets were produced at 5%, 10%, 15% volume ratios. After the produced billets were extruded and 5 mm thick plates were formed, tensile and fatigue crack propagation compact tensile (CT) samples were prepared. Optical microscope examinations were carried out to determine the microstructural properties of billet and samples. To determine the SiC particle–matrix interactions due to the composite microstructure, unlike the Al alloy, which affects the crack initiation life and crack propagation rate, detailed scanning electron microscopy (SEM) studies have been carried out.

Findings
Optical microscope examinations for the determination of the microstructural properties of billet and samples showed that although SiC particles were rarely clustered in the Al alloy matrix, they were generally homogeneously dispersed. Fatigue crack propagation rates were determined experimentally. While the highest crack initiation resistance was achieved at 5% SiC volume ratio, the slowest crack propagation rate in the stable crack propagation region was found in the unreinforced 2124 Al alloy. At volume ratios greater than 5%, the number of crack initiation cycles decreases and the propagation rate increases.

Originality/value
As a requirement of damage tolerance design, the fatigue crack propagation rate and fatigue behavior of materials to be used in high-tech vehicles such as aircraft structural parts should be well characterized. Therefore, safer use of these materials in critical structural parts becomes widespread. In this study, besides measuring fatigue crack propagation rates, the mechanisms causing crack acceleration or deceleration were determined by applying detailed SEM examinations.
How do employees’ strengths use for tasks and strengths use for relationships interact to influence their job performance?
Authors: Hai Shenyang , Park In-Jo 
Published: December 2023

Purpose
Drawing on prior research on strengths use and job performance, this study aims to investigate how employees’ strengths use for tasks and strengths use for relationships jointly influence role breadth self-efficacy and subsequent job performance, specifically in- and extra-role performances.

Design/methodology/approach
To test the assumptions, the authors methodologically performed a polynomial regression with response surface analysis using data collected from multiple time points and sources (i.e. 312 employee–supervisor dyads in Chinese companies).

Findings
The results showed that the higher the congruence between strengths use for tasks and strengths use for relationships, the higher the employees’ role breadth self-efficacy. Employees’ role breadth self-efficacy was greater when both strengths use for tasks and strengths use for relationships were high. Furthermore, the congruence between strengths use for tasks and strengths use for relationships had indirect effects on in- and extra-role performances via role breadth self-efficacy.

Originality/value
This study uniquely contributes to the strengths use literature by offering a more nuanced understanding of the consequences of strengths use for tasks and strengths use for relationships in the Chinese context. It highlights the importance of both types of strengths use for improving employee performance in Chinese organizations. Furthermore, this study provides new theoretical insights into the relationship between strengths use and job performance by ascertaining the mediating effect of role breadth self-efficacy.