bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drought resistance and improved yield result from modified malate metabolism in guard and vascular companion cells
Authors: Oitaven Pablo , Guindón María F. , Müller Gabriela L. , Margarit Ezequiel , Saper Carolina , Srebot María Sol , Fu Ying , Verma Karuna , Wewer Vera , Metzger Sabine , Lara María V. , Estavillo Gonzalo Martin , Maurino Veronica G. , Drincovich María F. 
Published: June 2024

AbstractDrought is a major threat to food security. Water loss through stomata is an inevitable consequence of CO2uptake, and water deficit inhibits plant growth, making it challenging to develop drought-resistant strategies without compromising yield. Here, we generated tobacco plants expressing a maize NADP-dependent malate decarboxylating enzyme in stomata and vascular cells (ME plants), which show higher seed yield and faster maturation compared to wild-type (WT) plants under normal irrigation and after drought. While WT plants die after 45 days of drought, ME plants survive without any adverse effects on seed production. In addition, ME plants exhibit improved photosynthetic efficiency despite reduced stomatal conductance and changes in stem morphology, which are likely related to their ability to withstand drought. We propose that enhanced C4-like biochemistry in cells surrounding the vascular system and increased sugar export likely compensated for the reduced stomatal conductance in ME plants. The study demonstrates that cell-targeted metabolic modifications can avoid pleiotropic effects and facilitate the stacking of beneficial traits to improve crop design.Significance StatementDrought is one of the biggest threats to global food security, and its impact on crop yield is expected to worsen due to climate change. Traditionally, drought resistance has often come at the expense of yield, creating a negative trade-off. However, we present here a promising solution to this challenge. We have developed a novel approach that successfully uncouples the negative balance between drought resistance and yield. By introducing a maize enzyme into specific tobacco cells, we have created drought-resistant plants with faster growth and higher seed yield. Most importantly, after prolonged drought, while the wild type dies, the modified plants maintain their high yield. This technology paves the way for greater food security and resilience to climate change.
A scalable computational framework for annotation-independent combinatorial target identification in scRNA-seq databases
Authors: Buser Maximilian , Marr Carsten 
Published: June 2024

AbstractThe applicability of novel targeted cell therapies is constrained by on-target off-tumor toxicities, posing significant challenges for safe and effective treatment. To develop strategies for mitigating these toxicities, a comprehensive understanding of the distribution of single-cell profiles across human tissues is essential. Single-cell RNA sequencing (scRNA-seq) provides detailed insights into cellular diversity and function. However, as data collection expands and RNA expression atlases comprise tens of millions of cells, effectively querying these databases to identify cell populations matching specific gene expression patterns becomes challenging. Key challenges include managing data volume, handling batch effects, navigating study-dependent data curation and annotation, and addressing the combinatorial complexity of possible target patterns. Userfriendly screening tools that allow for complex query target patterns without relying on existing annotations are currently missing. Here we presentotopia, a computational framework that enables fast queries of large scRNA-seq databases, enhancing the precision of cell population identification. Using precomputed neighborhood graphs and boolean logic for expression patterns,otopiaenables efficient queries addressing arbitrary combinatorial target patterns.otopiadoes not depend on cell type annotations and by exploiting unbiased expression pattern matching scores, it uncovers critical populations that annotation based methods overlook. We exemplifyotopia’s capabilities by identifying the largest B cell populations in the CELLxGENE census data using a CD19+CD22+CD5-query target pattern. Moreover, we show thatotopiacan provide a concise overview of cell populations matching hypothetical acute myeloid leukemia (AML) dual targets, realizing logic AND gates, across different tissues.otopiaenables the estimation of ontarget off-tumor toxicities for drugs targeting both single markers and complex marker combinations, surpassing previous methods that focus mainly on single markers. With the expanding availability of scRNA-seq data,otopiarepresents a scalable, unbiased, and automated approach to refine putative therapeutic targets in order to minimize toxicities.
Expansions of Price Equation for Viability and Fecundity Selection
Authors: Han Jia-Xu , Wang Rui-Wu 
Published: June 2024

AbstractThe Price equation offers a means of separating the portion of population change attributable to natural selection from the overall change. There is debate over the universality of the Price equation due to the belief that it makes simple assumptions. However, it should be noted that the definition of fitness is assumed within the Price equation. To account for populations subject to viability selection and fecundity selection during their life cycle, two expansions of the Price equation have been proposed based on a clear understanding of fitness. These expansions include three terms: a viability selection term, a fecundity selection term, and a mean value term that captures the difference between adults and their zygotes. Unlike the classic Price equation, which also has a mean value term capturing the difference between adults and their successful zygotes, the mean value term in our expansions will be zero in the absence of mutation, drift, and recombination. Furthermore, the individual-based simulation shows that our expansions can outperform the classic Price equation in capturing the average change in strategy for resource allocation. In summary, our expansions fully capture the effects of natural selection and separate them into viability and fecundity selection terms. Our expansions allows for a wider application of the Price equation, especially in the case where there is a trade-off between viability and fecundity selection.
Simply crushedZizyphi spinosi semenprevents neurodegenerative diseases and reverses age-related cognitive decline in mice
Authors: Umeda Tomohiro , Sakai Ayumi , Uekado Rumi , Shigemori Keiko , Nakajima Ryota , Yamana Kei , Tomiyama Takami 
Published: June 2024

AbstractNeurodegenerative diseases are age-related disorders characterized by the cerebral accumulation of amyloidogenic proteins, and cellular senescence underlies their pathogenesis. Thus, it is necessary for preventing these diseases to remove toxic proteins, repair damaged neurons, and suppress cellular senescence. As a source for such prophylactic agents, we selectedZizyphi spinosi semen(ZSS), a medicinal herb used in traditional Chinese medicine. ZSS hot water extract ameliorated Aβ and tau pathology and cognitive impairment in mouse models of Alzheimer’s disease and frontotemporal dementia. Non-extracted ZSS simple crush powder showed stronger effects than the extract and improved α-synuclein pathology and cognitive/motor function in Parkinson’s disease model mice. Furthermore, when administered to normal aged mice, the ZSS powder suppressed cellular senescence, reduced DNA oxidation, promoted brain-derived neurotrophic factor expression and neurogenesis, and enhanced cognition to levels similar to those in young mice. The quantity of known active ingredients of ZSS, jujuboside A, jujuboside B, and spinosin, was not proportional to the nootropic activity of ZSS. These results suggest that ZSS simple crush powder is a promising dietary material for the prevention of neurodegenerative diseases and brain aging.Impact statementNon-extracted simple crush powder ofZizyphi spinosi semenhas not only disease-preventing effects but also brain-rejuvenating effects in mice.
Semantic Influences on Object Detection: Drift Diffusion Modeling Provides Insights Regarding Mechanism
Authors: Xue Jingming , Wilson Robert C. , Peterson Mary A. 
Published: June 2024

AbstractResearch shows that semantics, activated by words, impacts object detection. Skocypec & Peterson (2022) indexed object detection via correct reports of where figures lie in bipartite displays depicting familiar objects on one side of a border. They reported 2 studies with intermixed Valid and Invalid labels shown before test displays and a third, control, study. Valid labels denoted display objects. Invalid labels denoted unrelated objects in a different or the same superordinate-level category in studies 1 & 2, respectively. We used drift diffusion modeling (DDM) to elucidate the mechanisms of their results. DDM revealed that, following Valid labels, drift rate toward the correct decision increased, i.e., SNR increased. Following Invalid labels, SNR was lower only for upright displays in study 2. Thresholds were higher in studies 1 & 2 than in control. That more evidence must be accumulated from displays that follow labels implies that familiar object detection entails semantic activation. Threshold was even higher following Invalid labels in study 2, suggesting that more evidence from the display is needed to resolve within- category conflicts. These results support the view that semantic networks are engaged in object detection.
Human induced pluripotent stem cell-derived microglia contribute to the pathophysiology of Fragile X syndrome via increased RAC1 signaling
Authors: Banerjee Poulomi , Sharma Shreya Das , Burr Karen , Morris Kimberley , Ritakari Tuula , Baxter Paul , Cooper James D , Cardinalli Alessandra , Subash Srividya , Paza Evdokia , Story David , Chattarji Sumantra , Kind Peter C , Carragher Neil O , Selvaraj Bhuvaneish T , Priller Josef , Chandran Siddharthan 
Published: June 2024

AbstractFragile X syndrome (FXS) is one of the most common monogenic causes of neurodevelopmental disorders characterized by intellectual disability, autism and epilepsy. Emerging evidence suggests a role for immune dysfunction in autism. Using induced pluripotent stem cell (iPSC)-derived microglial cells from FXS patients (mFXS-MG) andFMR1-deficient microglia fromFMR1-knock out human embryonic stem cells (FMR1 KO-MG), we show that loss-of-function of Fragile X Messenger Ribonucleoprotein (FMRP) leads to cell autonomous phagocytic deficits and a proinflammatory state in microglia when compared to gene-corrected controls. Moreover, increased RAC1 signaling in mFXS-MG andFMR1 KO-MG results in increased actin polymerization and enhanced activation of NF-κB signaling. Exposure of control iPSC-derived cortical neuron cultures to conditioned medium from proinflammatory mFXS-MG results in hyperexcitability. Importantly, pharmacological inhibition of RAC1 signaling in mFXS-MG attenuates their proinflammatory profile and corrects the neuronal hyperexcitability caused by the conditioned medium. Our results suggest that microglia impair neuronal function in FXS, which can be prevented by targeting of RAC1 signaling.Significance statementFXS is one of the most common monogenic causes of neurodevelopmental disorders characterized by intellectual disability, autism, epilepsy and has been associated with immune dysfunction. We therefore generated brain macrophages (microglia) from patient-derived induced pluripotent stem cells (mFXS-MG) and an embryonic stem cell line deficient in the Fragile X messenger ribonucleoprotein 1 (FMR1KO-MG). We find enhanced activation of RAC1 signaling resulting in phagocytic deficits and immune activation of mFXS-MG andFMR1KO-MG. Exposure of control iPSC-derived cortical neurons to conditioned medium from proinflammatory mFXS-MG results in neuronal hyperexcitability, which can be prevented by pharmacological RAC1 inhibition in mFXS-MG. We conclude that RAC1 signaling in microglia could be a potential therapeutic target in FXS.
Behavioral and neural mechanisms of face-specific attention during goal-directed visual search
Authors: Zhang Jie , Zhu Xiaocang , Zhou Huihui , Wang Shuo 
Published: June 2024

AbstractGoal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus non-faces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network while macaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search, but were differentially engaged by face and house targets. V4 and IT category-selective units also encoded fixation transitions and search dynamics. Compared to distractors, fixations on targets reduced spike-LFP coherence within the temporal cortex. Importantly, target-induced desynchronization between the temporal and prefrontal cortices was only evident for face targets, suggesting that attention to faces differentially engaged the prefrontal cortex. We further revealed bidirectional theta influence between the temporal and prefrontal cortices using Granger causality, which was again disproportionate for faces. Finally, we showed that the search became more efficient with increasing target-induced desynchronization. Together, our results suggest domain specificity for attending to faces and an intricate interplay between visual attention and social processing neural networks.
Complexome profiling of the Chlamydomonaspsb28mutant reveals THYLAKOID ENRICHED FRACTION 5 as an early photosystem II assembly factor
Authors: Lang Julia , König Katharina , Venn Benedikt , Spaniol Benjamin , Spaniol Lara , Sommer Frederik , Mustas Matthieu , Geimer Stefan , Fürtges Torben , Brzezowski Pawel , Zabret Jure , Wollman Francis-André , Nowacyzk Mark , Scheuring David , Rudack Till , Mühlhaus Timo , Choquet Yves , Schroda Michael 
Published: June 2024

AbstractSeveral auxiliary factors are required for the assembly of photosystem (PS) II, one of which is Psb28. While the absence of Psb28 in cyanobacteria has little effect on PSII assembly, we show here that the Chlamydomonaspsb28-null mutant is severely impaired in PSII assembly, showing drastically reduced PSII supercomplexes, dimers and monomers, while overaccumulating RCII, CP43modand D1mod. The mutant had less PSI and more Cytb6fand showed fewer thylakoid stacks and distorted chloroplast morphology. Complexome profiling of thepsb28mutant revealed that TEF5, the homolog of Arabidopsis PSB33/LIL8, co-migrated particularly with RCII. TEF5 also interacted with PSI. A Chlamydomonastef5null mutant is also severely impaired in PSII assembly and overaccumulates RCII and CP43mod. RC47 was not detectable in the light-growntef5mutant. Our data suggest a possible role for TEF5 in facilitating the assembly of CP47modinto RCII. Both thepsb28andtef5mutants exhibited decreased synthesis of CP47 and PsbH, suggesting negative feedback regulation possibly exerted by the accumulation of RCII and/or CP43modin both mutants. The strong effects of missing auxiliary factors on PSII assembly in Chlamydomonas suggest a more effective protein quality control system in this alga than in land plants and cyanobacteria.One-sentence summaryThe Chlamydomonas psb28 mutant is severely impaired in PSII assembly which via complexome profiling allowed identifying TEF5 as a novel PSII assembly factor that likely facilitates CP47 assembly.The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (https://academic.oup.com/plcell/pages/General-Instructions) is: Michael Schroda (m.schroda@rptu.de).
Cell-specific wiring routes information flow through hippocampal CA3
Authors: Watson Jake F. , Vargas-Barroso Victor , Jonas Peter 
Published: June 2024

AbstractThe hippocampus is dogmatically described as a trisynaptic circuit. Dentate gyrus granule cells, CA3 pyramidal neurons (PNs), and CA1 PNs are serially connected, forming a circuit that critically enables memory storage in the brain. However, fundamental aspects of hippocampal function go beyond this simplistic ‘trisynaptic’ definition. CA3 PNs connect not only to CA1, but also establish the largest autoassociative network in the brain. In addition, CA3 PNs are not uniform, differing in their morphology, intrinsic properties, and even the extent of granule cell input. Understanding how these different subtypes of CA3 PNs are embedded in the hippocampal network is essential for our quest to understand learning and memory. Here, we performed simultaneous multi-cellular patch-clamp recordings from up to eight CA3 PNs in acute mouse hippocampal slices, testing 3114 possible connections between identified cells. Combined with post-hoc morphological analysis, this allowed full characterization of neuronal heterogeneity in functioning microcircuits. We demonstrate that CA3 PNs can be divided into distinct ‘deep’ and ‘superficial’ subclasses, with altered input-output balance. While both subtypes formed recurrent connectivity within classes, connectivity between subtypes was surprisingly asymmetric. Recurrent connectivity was abundant from superficial to deep, but almost absent from deep to superficial PNs, thereby splitting CA3 into parallel recurrent networks which will allow more complex information processing. Finally, we observed innervation of PN subclasses by distinct interneurons, a potential mechanism to gate information flow through CA3 sublayers. Together, our data present a major revision to the classical ‘trisynaptic’ view of the hippocampus, bringing us closer to understanding its complex action in information storage.
Ciselement length variability does not confer differential transcription factor occupancy at theD. melanogasterhistone locus
Authors: Hodkinson L.J. , Rieder L.E. 
Published: June 2024

AbstractHistone genes require precise regulation to maintain histone homeostasis and ensure nucleosome stoichiometry. Animal histone genes often have unique clustered genomic organization. However, there is variability of histone gene number and organization as well as differential regulation of the histone genes across species. TheDrosophila melanogasterhistone locus has unique organizational characteristics as it exists as a series of ∼100 highly regular, tandemly repeated arrays of the 5 replication-dependent histone genes at a single locus. YetD. melanogasterare viable with only 12 transgenic histone gene arrays. We hypothesized that the histone genes across the locus are differentially regulated. We discovered that the GA-repeat within theH3/H4promoter is the only variable sequence across the histone gene arrays. TheH3/H4promoter GA-repeat is targeted by CLAMP to promote histone gene expression. We also show two additional GA-binding transcription factors, GAGA Factor and Pipsqueak, target the GA-repeat. When we further examined CLAMP and GAF targeting, we determined that neither CLAMP nor GAF show bias for any GA-repeat lengths. Furthermore, we found that the distribution of GA-repeats targeted by both CLAMP and GAF do not change throughout early development. Together our results suggest that the transcription factors targeting theH3/H4GA-repeat do not impact differential regulation of the histone genes, but indicate that future studies should interrogate additionalciselements or factors that impact histone gene regulation.
MYB transcription factor, NtMYB308, regulates anthocyanin and lignin content, and fungal tolerance in tobacco
Authors: Singh Nivedita , Dwivedi Shambhavi , Singh Deeksha , Pathak Pranshu Kumar , Trivedi Prabodh Kumar 
Published: June 2024

AbstractAnthocyanins are secondary metabolites synthesized through the phenylpropanoid pathway. They attract pollinators, possess antioxidant properties that scavenge free radicals during environmental stress, and provide protection against various stress conditions. Lignin, another secondary metabolite, plays crucial roles in providing mechanical support, facilitating water and solute transport, and protecting against pathogens. MYB transcription factors, particularly R2R3 MYBs, are key regulators of secondary metabolism, especially within the phenylpropanoid pathway. These factors act as both activators and repressors. The N-terminal region of R2R3-MYB repressors contains a conserved bHLH-binding domain, while the C-terminal domain is divergent and includes an EAR repressor domain. R2R3-MYB proteins notably target sequences such as the MYB-response element and AC elements. In this study, we identified and characterized the Nicotiana MYB transcription factor, NtMYB308, and explored its regulatory function in anthocyanin and lignin biosynthesis in tobacco. Our Virus Induced Gene Silencing (VIGS) and Protein-DNA interaction studies suggest that NtMYB308 is a negative regulator of anthocyanin and lignin biosynthesis by binding to the promoters of genes involved in these pathways. To validate our findings, we developed CRISPR/Cas9-based knockout mutant plants of tobacco,NtMYB308CR, which showed up-regulation of anthocyanin and lignin biosynthesis. Conversely, NtMYB308 overexpression (NtMYB308OX) plants exhibited the opposite effect. Enhanced anthocyanin and lignin levels inNtMYB308CRplants provided tolerance against the fungusAlternaria solani, while NtMYB308OX lines were susceptible. This study advances our understanding of the regulatory mechanisms governing anthocyanin and lignin biosynthesis and their role in biotic stress in tobacco.One Sentence SummaryA R2R3 MYB transcription factor, NtMYB308, negatively regulates anthocyanin and lignin content, and fungal tolerance in tobacco.
Sequential estimation of nonstationary oscillator states and stimulus responses
Authors: Nelson Joseph N. , Widge Alik S. , Netoff Théoden I. 
Published: June 2024

AbstractNeural oscillations have been linked to multiple behaviors and neuropsychiatric disorders. The individual contributions to behavior from both oscillations and non-oscillatory activity are still unclear, complicating efforts to link neurophysiology to cognition, hindering the discovery of novel biomarkers, and preventing the development of effective therapeutics. To overcome these hurdles, it will be critical to investigate the biological origins of neural oscillations by characterizing the dynamic properties of different brain regions. The dynamical regime for a population of neurons generating oscillations in neural recordings can be discovered by stimulating the population and recording its subsequent response to stimulation. There are different dynamical regimes that can produce population-level neural oscillations. For certain dynamical regimes, like that of a nonlinear oscillator, the phase response curve (PRC) can help differentiate the dynamic state of the population. The PRC can be measured by stimulating the population across different phases of its oscillatory state. However, neural dynamics are non-stationary, so neural oscillations will vary in frequency and amplitude across a recording and the PRC can change over time. This non-stationarity could bias a PRC estimated from an electrophysiological experiment, preventing accurate characterization of a neural population’s dynamics. This necessitates tools that can operate online to trigger stimulation and update PRC estimates. To that end, we develop online methods for tracking non-stationary oscillations and recovering PRCs corrupted by estimation errors. We validate the performance of our non-stationary oscillation estimator compared to both a known ground truth model and an alternative phase estimation approach. We demonstrate that a PRC can be recovered online underdifferent random error conditionsin silicoand that a similar amplitude response curve (ARC) can be estimated from physiologic data using online methods compared to offline approaches.