bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-linear stress-softening of the bacterial cell wall confers cell shape homeostasis
Authors: Bardetti Paola , Barber Felix , Rojas Enrique R. 
Published: September 2024

AbstractThe bacillus - or rod - is a pervasive cellular morphology among bacteria. Rod-shaped cells elongate without widening by reinforcing their cell wall anisotropically to prevent turgor pressure from inflating cell width. Here, we demonstrate that a constrictive force is also essential for avoiding pressure-driven widening in Gram-positive bacteria. Specifically, super-resolution measurements of the nonlinear mechanical properties of the cell wall revealed that across a range of turgor pressure cell elongation directly causes width constriction, similar to a “finger trap” toy. As predicted by theory, this property depends on cell-wall anisotropy and is precisely correlated with the cell’s ability to maintain a rod shape. Furthermore, the acute non-linearities in the dependence between cell length and width deformation result in a negative-feedback mechanism that confers cell-width homeostasis. That is, the Gram-positive cell wall is a “smart material” whose exotic mechanical properties are exquisitely adapted to execute cellular morphogenesis.
Stimulus repetition induces a two-stage learning process in primary visual cortex
Authors: Cui Lihan , Bo Ke , Xiong Changhao , Keil Andreas , Ding Mingzhou 
Published: September 2024

AbstractRepeated stimulus exposure alters the brain’s response to the stimulus. We investigated the underlying neural mechanisms by recording functional MRI data from human observers passively viewing 120 presentations of two Gabor patches (each Gabor repeating 60 times). We evaluated support for two prominent models of stimulus repetition, the fatigue model and the sharpening model. Our results uncovered a two-stage learning process in the primary visual cortex. In Stage 1, univariate BOLD activation in V1 decreased over the first twelve repetitions of the stimuli, replicating the well-known effect of repetition suppression. Applying MVPA decoding along with a moving window approach, we found that (1) the decoding accuracy between the two Gabors decreased from above-chance level (∼60% to ∼70%) at the beginning of the stage to chance level at the end of the stage (∼50%). This result, together with the accompanying weight map analysis, suggested that the learning dynamics in Stage 1 were consistent with the predictions of the fatigue model. In Stage 2, univariate BOLD activation for the remaining 48 repetitions of the two stimuli exhibited significant fluctuations but no systematic trend. The MVPA decoding accuracy between the two Gabor patches was at chance level initially and became progressively higher as stimulus repetition continued, rising above and staying above chance level starting at the ∼35th repetition. Thus, results from the second stage supported the notion that sustained and prolonged stimulus repetition prompts sharpened representations. Additional analyses addressed (1) whether the neural patterns within each learning stage remained stable and (2) whether new neural patterns were evoked in Stage 2 relative to Stage 1.
Bacterial transcriptional repressor NrdR – a flexible multifactorial nucleotide sensor
Authors: Rozman Grinberg Inna , Bimaï Ornella , Shahid Saher , Philipp Lena , Martínez-Carranza Markel , Banerjee Ipsita , Lundin Daniel , Stenmark Pål , Sjöberg Britt-Marie , Logan Derek T. 
Published: September 2024

AbstractNrdR is a bacterial transcriptional repressor consisting of a Zn-ribbon domain followed by an ATP-cone domain. Understanding its mechanism of action could aid the design of novel antibacterials. NrdR binds specifically to two “NrdR boxes” upstream of ribonucleotide reductase operons, of whichEscherichia colihas three: nrdHIEF, nrdDG and nrdAB, where we identified a new box. We show thatE. coliNrdR (EcoNrdR) has similar binding strength to all three sites when loaded with ATP plus dATP or equivalent diphosphate combinations. No other combination of nucleotides promotes binding to DNA. We present crystal structures of EcoNrdR-ATP-dATP and EcoNrdR-ADP-dATP, which are the first high-resolution crystal structures of an NrdR. We have also determined cryo-EM structures of DNA-bound EcoNrdR-ATP-dATP and novel filaments of EcoNrdR-ATP. Tetrameric forms of EcoNrdR involve alternating interactions between pairs of Zn-ribbon domains and ATP-cones. The structures reveal considerable flexibility in relative orientation of ATP-cones vs Zn-ribbon domains. The structure of DNA-bound EcoNrdR-ATP-dATP shows that significant conformational rearrangements between ATP-cones and Zn-ribbons accompany DNA binding while the ATP-cones retain the same relative orientation. In contrast, ATP-loaded EcoNrdR filaments show rearrangements of the ATP-cone pairs and sequester the DNA-binding residues of NrdR such that they are unable to bind to DNA. Our results, in combination with a previous structural and biochemical study, point to highly flexible EcoNrdR structures that when loaded with the correct nucleotides adapt to an optimal promoter binding conformation.
The Arabidopsis RS2Z32 and RS2Z33 proteins are dynamic splicing factors whose RNA recognition motif (RRM) domain contributes to protein-protein and protein-RNA interactions
Authors: Fanara Steven , Schloesser Marie , Gérard Méline , De Franco Simona , Vandevenne Marylène , Hanikenne Marc , Motte Patrick 
Published: September 2024

AbstractThe Arabidopsis splicing factors arginine/serine-rich zinc knuckle-containing proteins 32 and 33 (RS2Z32 and RS2Z33) are plant-specific members of the SR family whose molecular functions received little attention. Here, we characterized both RS2Z32 and RS2Z33 by examining their expression profile at different stages of development and their spatial cellular distribution, as well as the contribution of their domains in the establishment of protein-protein interactions and RNA binding specificity. We report that theRS2Z32andRS2Z33promoters are ubiquitously active during vegetative and reproductive growth, and that both RS2Z splicing factors localize in the nucleus (except the nucleolus). We show that the C-terminal arginine/serine-rich (RS) domain, but not the serine/proline-rich (SP) extension, is a determinant of nuclear localization, which likely requires phosphoresidues putatively phosphorylated by kinases of the SRPK family. We demonstrate that their RNA recognition motif (RRM) domain specifically binds pyrimidine-rich RNA motifs via three residues (Y14, Y46, F48), and is also involved in protein-protein interactions with at least three SR proteins, namely SR45, SCL30, and SR34. Finally, we show that mutations in RNA-binding domains (i.e. RRM and zinc knuckles, ZnKs) affect the nucleocytoplasmic dynamics of both RS2Z proteins. Our findings provide molecular evidence for the involvement of plant-specific SR splicing factors into the regulation of the splicing process.HighlightSpecific domains of theArabidopsisRS2Z splicing factors contribute to their nuclear localization, nucleocytoplasmic dynamics, and ability to contact protein partners and specific pyrimidine-rich RNA motifs.
Calibration of FRET-based biosensors using multiplexed biosensor barcoding
Authors: Wu Jhen-Wei , Yang Jr-Ming , Chen Chao-Cheng , Au Gabriel , Wang Suyang , Chern Gia-Wei , Huang Chuan-Hsiang 
Published: September 2024

AbstractFörster resonance energy transfer (FRET) between fluorescent proteins (FPs) is widely used in the design of genetically encoded fluorescent biosensors, which are powerful tools for monitoring the dynamics of biochemical activities in live cells. FRET ratio, defined as the ratio between acceptor and donor signals, is often used as a proxy for the actual FRET efficiency, which must be corrected for signal crosstalk using donor-only and acceptor-only samples. However, the FRET ratio is highly sensitive to imaging conditions, making direct comparisons across different experiments and over time challenging. Inspired by a method for multiplexed biosensor imaging using barcoded cells, we reasoned that calibration standards with fixed FRET efficiency can be introduced into a subset of cells for normalization of biosensor signals. Our theoretical analysis indicated that the FRET ratio of high-FRET species relative to non-FRET species slightly decreases at high excitation intensity, suggesting the need for calibration using both high and low FRET standards. To test these predictions, we created FRET donor-acceptor pairs locked in “FRET-ON” and “FRET-OFF” conformations and introduced them into a subset of barcoded cells. Our results confirmed the theoretical predictions and showed that the calibrated FRET ratio is independent of imaging settings. We also provided a strategy for calculating the FRET efficiency. Together, our study presents a simple strategy for calibrated and highly multiplexed imaging of FRET biosensors, facilitating reliable comparisons across experiments and supporting long-term imaging applications.
Neighbor sensing through rhizodeposits in sorghum affects plant physiology and productivity
Authors: Ben-Zeev Shiran , Penn Amanda , Lawrence-Paul Erica H. , Abrams Desa Rae , Ben-Zeev Rotem , Lowry Carolyn , Lasky Jesse R. 
Published: September 2024

AbstractPlant-plant interactions play a crucial role in shaping the growth environment for crops, impacting their productivity and stress response. The interaction between plants aboveground has been studied and incorporated into breeding programs that select for plants that reduce aboveground competition between plants. However, few studies have focused on belowground interactions, and these looked at combined interactions and root partitioning in the soil. This study focuses on the developmental and physiological responses of sorghum (Sorghum bicolorL.) genotypes to neighboring sorghum plants. In this study, we used two growing methods: i) a focal plant surrounded by neighboring plants in the same pot but without shading, and ii) a focal plant grown either alone or surrounded by neighbors, irrigated with nutrient solution passed through pots (leachates) with or without plants. Our results showed that the presence of neighbors in the same pot led to reduced size-dry weight height, and leaf area of the focal plant. In addition, the presence of neighbors reduced stomatal conductance and PSII quantum yield. While the response direction was similar across tested genotypes, the magnitude varied. The results were repeated when neighboring plants were not grown in the same pot, but the nutrient solution passed through the root system of plants of the neighboring genotype. Furthermore, we saw a reduction in assimilation rate and stomatal conductance when plants were exposed to either the physical presence of neighbors or leachate. We did not find differences in root architecture in either treatment. These results show plants change their growth in response to neighbors and that the signal is carried through the liquid phase of the soil. Our findings provide insights into sorghum plants’ responses to below-ground signaling from neighboring plants and lay the foundation for future studies enabling increased crop performance under high-density planting conditions.
Systemic in utero gene editing as a treatment for cystic fibrosis
Authors: Ricciardi Adele S. , Barone Christina , Putman Rachael , Quijano Elias , Gupta Anisha , Nguyen Richard , Mandl Hanna , Piotrowski-Daspit Alexandra S. , Lopez-Giraldez Francesc , Luks Valerie , Freedman-Weiss Mollie R. , Farrelly James , Ahle Samantha , Glazer Peter M. , Saltzman W. Mark , Stitelman David H. , Egan Marie E. 
Published: September 2024

AbstractIn utero gene editing has the potential to modify disease causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. In cystic fibrosis (CF), a disease that arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. Thus, treating CF patients early is crucial for preventing or delaying irreversible organ damage. Here we demonstrate proof-of-concept of multiorgan mutation correction in CF using peptide nucleic acids (PNAs) encapsulated in polymeric nanoparticles and delivered systemically in utero. In utero editing was associated with sustained postnatal CFTR activity, at a level similar to that of wild-type mice, in both respiratory and gastrointestinal tissue, without detection of off-target mutations in partially homologous loci. This work suggests that systemic in utero gene editing represents a viable strategy for treating monogenic diseases before birth that impact multiple tissue types.
Acetylation of lysine 82 initiates TDP-43 nuclear loss of function by disrupting its nuclear import
Authors: Zhang Sitao , Vazquez-Sanchez Sonia , Lu Shan , Baughn Michael W. , Lim Jaisen , Oung Spencer , Gao Lilian , Diedrich Jolene K. , Yates John R , Yu Haiyang , Ravits John , Cleveland Don W. 
Published: September 2024

AbstractThe hallmark of a spectrum of age-dependent neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS), is a TDP-43 proteinopathy that includes nuclear loss of function and cytoplasmic aggregation. Here, reduced proteasome activity, as naturally occurs during aging, is shown to inhibit nuclear import of TDP-43. Quantitative mass spectrometry is used to determine that TDP-43 is the protein whose nuclear localization is most perturbed upon reduction in proteasome activity, culminating in elevated cytoplasmic TDP-43. Interaction of importin-α1 with the bipartiteclassicalnuclear localizationsequence (cNLS) of TDP-43 is shown to be disrupted by partial proteasome inhibition but maintained by replacement with a PY-NLS that is recognized by importin-β2. Mechanistically, this nuclear depletion of TDP-43 is shown to be driven by ubiquitination or acetylation of lysines 79, 82, and 84 within the cNLS when proteasome activity is reduced in human neurons. Specifically, acetylation at lysine 82 is sufficient to abolish TDP-43 binding to importin-α1 and subsequent nuclear import of TDP-43. Moreover, using acetylation-specific TDP-43 antibodies, we detected acetylation of lysine 82 in the motor cortex of sporadic ALS patients but not control subjects. Our findings demonstrate that post-translational acetylation at lysine 82 of TDP-43 drives disruption of its importin-α1-mediated nuclear import and is sufficient to initiate TDP-43 nuclear loss of function and cytoplasmic accumulation, evidence supporting acetylation as a plausible initiator of TDP-43 proteinopathies.
Biologically-Constrained Spiking Neural Network for Neuromodulation in Locomotor Recovery after Spinal Cord Injury
Authors: Chia Raymond , Lin Chin-Teng 
Published: September 2024

Presynaptic inhibition after spinal cord injury (SCI) has been hypothesised to disproportionately affect flexion reflex loops in locomotor spinal circuitry. Reducing gamma-aminobutyric acid (GABA) inhibitory activity increases the excitation of flexion circuits, restoring muscle activation, and stepping ability. Conversely, nociceptive sensitisation and muscular spasticity can emerge from insufficient GABAergic inhibition. To investigate the effects of neuromodulation and proprioceptive sensory afferents in the spinal cord, a biologically constrained spiking neural network (SNN) was developed. The network describes the flexor motoneuron (MN) reflex loop with inputs from ipsilateral Ia- and II-fibres and tonically firing interneurons. The model was tuned to a baseline level of locomotive activity before simulating an inhibitory-dominant and body-weight supported (BWS) SCI state. Electrical stimulation (ES) and serotonergic agonists were simulated by the excitation of dorsal fibres and reduced conductance in excitatory neurons. ES was applied across all afferent fibres without phase- or muscle-specific protocols. The present study describes, for the first time, the release of GABAergic inhibition on flexor MNs as a potential mechanism underlying BWS treadmill training. The results demonstrate the synaptic mechanisms by which neuromodulatory therapy tunes the excitation and inhibition of ankle flexor MNs during locomotion for smoother and more coordinated movement.Author SummarySCI is a life-altering condition that often leaves young adults paralysed and reliant on others for support. Restoring the ability to walk is a critical goal to help improve independence and quality of life for people living with SCI. Promising new treatments, such as spinal cord stimulation and drug therapies, aim to reawaken the neurons that control walking. However, scientists still do not entirely understand how these treatments work. In this study, we developed a detailed computer model of the neural circuits involved in walking to test how therapies such as serotonin-boosting drugs, ES, and BWS training might help. Our findings suggest that these treatments can work together to reduce excessive inhibition that blocks ankle movement, leading to smoother and more coordinated steps. This research helps uncover how these therapies work and provides insights to develop better rehabilitation strategies for improving walking after SCI.
Gray matter volume increase in the retrosplenial/posterior cingulate cortices of blind soccer players
Authors: Morita Tomoyo , Naito Eiichi 
Published: September 2024

AbstractSpatial navigation is a crucial brain function that occurs when an individual moves from one location to another. This function normally relies on vision, and the retrosplenial/posterior cingulate cortices (RSC/PCC) and parahippocampal cortex (PHC) play crucial roles. However, an extraordinary adaptation can be observed in blind soccer players, where the human brain can perform spatial navigation without vision. Therefore, this study tested the possible increase in gray matter (GM) volume in the RSC/PCC and PHC in the brains of a world’s top blind soccer player and other blind soccer players. We collected structural magnetic resonance imaging (MRI) scans from six blind soccer players (including the world’s top player) and eight blind non-soccer players. Using voxel-based morphometry (VBM) analysis (single-case VBM approach), we examined GM volume increase in each participant compared to 250 sighted participants (all of whom had never played blind soccer). Compared with the sighted participants, the world’s top blind soccer player had a significant increase in GM volume in the bilateral RSC/PCC. Two of the other five blind soccer players also showed an increase in the left RSC/PCC. However, such an increase in GM volume was not observed in the blind non-soccer players. Eventually, the probability of a significant increase in the RSC/PCC was significantly higher in the blind soccer group than in the blind non-soccer group. In contrast, only one blind soccer player (not the top player) showed a significant increase in the PHC, and no between-group difference was observed in the probability of a significant increase in the PHC. This study, unveiling the characteristics of the brains of the world’s top blind soccer player and of other blind soccer players, for the first time demonstrates that blind soccer training, which requires spatial navigation based on non-visual cues, may enlarge the human RSC/PCC and provide findings that promote understanding the brains of challenged persons playing blind soccer.
Recombination shapes the diversification of thewtfmeiotic drivers
Authors: Wang Yan , Xu Hao , He Qinliu , Wu Zhiwei , Gong Zhen , Han Guan-Zhu 
Published: September 2024

AbstractMeiotic drivers are selfish genetic elements that distort fair segregation. Thewtfgenes are poison-antidote meiotic drivers that are experiencing rapid diversification in fission yeasts. However, gene duplication alone is insufficient to drive the diversification ofwtfgenes, given the poison encoded by a newly duplicatedwtfgene can be detoxified by the antidote encoded by the originalwtfgene. Here, we analyze the evolution ofwtfgenes across 21 strains ofSchizosaccharomyces pombe. Knocking out each of 25wtfgenes inS. pombestrain 972h- separately does not attenuate the yeast growth, indicating that thewtfgenes might be largely neutral to their carriers in asexual life cycle. Interestingly,wtfgenes underwent recurrent and intricate recombination. As proof-of-principle, we generate a novel meiotic driver through artificial recombination betweenwtfdrivers, and its encoded poison cannot be detoxified by the antidotes encoded by their parentalwtfgenes but can be detoxified by its own antidote. Therefore, we propose that recombination can generate new meiotic drivers and thus shape the diversification of thewtfdrivers.
A novel channel invariant architecture for the segmentation of cells and nuclei in multiplexed images using InstanSeg
Authors: Goldsborough Thibaut , O’Callaghan Alan , Inglis Fiona , Leplat Léo , Filby Andrew , Bilen Hakan , Bankhead Peter 
Published: September 2024

AbstractThe quantitative analysis of bioimaging data increasingly depends on the accurate segmentation of cells and nuclei, a significant challenge for the analysis of high-plex imaging data. Current deep learning-based approaches to segment cells in multiplexed images require reducing the input to a small and fixed number of input channels, discarding imaging information in the process. We present Channel Net, a novel deep learning architecture for generating three-channel representations of multiplexed images irrespective of the number or ordering of imaged biomarkers. When combined with InstanSeg, ChannelNet sets a new benchmark for the segmentation of cells and nuclei on public multiplexed imaging datasets. We provide an open implementation of our method and integrate it in open source software. Our code and models are available onhttps://github.com/instanseg/instanseg.
Discovery of a newPhenuivirusspecies inLachenaliaplants reveals possible co-evolution between 5’ and 3’ RNA sequence motifs
Authors: Dekker Rob J. , de Leeuw Wim C. , van Olst Marina , Ensink Wim A. , van Leeuwen Selina , Breit Timo M. , Jonker Martijs J. 
Published: September 2024

AbstractThis study reports the discovery of a new Phenuivirus species, named Lachenalia Phenuivirus-1 (LacPhV-1), from Lachenalia plants in an urban botanic garden in Amsterdam. Using a combination of smallRNA-seq, RNA-seq, and advanced bioinformatics, we identified a segmented negative-strand RNA virus in the Phenuiviridae family. Our findings show significant divergence between this new virus and known Phenuiviruses, such as Tulip Streak Virus (TuSV) and Lactuca Big Vein associated Phlebovirus (LBVaPV), supporting its classification as a distinct species. Notably, the sequence differences found in the conserved 5’ and 3’ ends of these segments suggest potential co-evolution. Despite the observed genomic distances, there is significant conservation in the RdRp subdomain, underscoring evolutionary relationships among LacPhV-1, TuSV, and LBVaPV. Our findings expand the known global virome and highlight the importance of exploring plant viromes in diverse ecological settings to better understand virus evolution and diversity.