bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene flow from Fraxinus cultivars into natural stands of Fraxinus pennsylvanica occurs range-wide, is regionally extensive, and is associated with a loss of allele richness
Authors: Abhainn Everett A. , Shirley Devin L. , Stanley Robert K. , Scarpato Tatum , Koch Jennifer L. , Romero-Severson Jeanne 
Published: November 2023

AbstractIn North America, the ubiquitous planting of a comparatively small number ofFraxinus(ash) cultivars in both urban and rural environments over the last 70-80 years may have permitted extensive gene flow into naturally regenerated stands. In the light of multiple biotic threats to the North AmericanFraxinus, an assessment of the extent of gene flow from ash cultivars and the current state of genetic diversity inF. pennsylvanica(green ash), one of the most widely distributed species, is needed to inform seed collection strategies for the preservation of genetic diversity range-wide. We used 16 EST-SSR markers to genotype 1291 trees from 48 naturally regenerated populations of green ash across the native range, 19F. pennsylvanicacultivars and oneF. americana(white ash) cultivar. We detected first generation cultivar parentage with high confidence in 172 individuals in 34 of the 48 populations and extensive cultivar parentage (23-50%) in eight populations. The incidence of cultivar parentage was negatively associated with allele richness (R2= 0.151, p = 0.006). The high frequency of cultivar propagule dispersal in our study suggests that a significant proportion of the standing genetic variation in local populations may not be of local origin, a result that has serious implications for the study of adaptive variation and the conservation of theFraxinusgene pool.
Quantitative Cross-Species Comparison of Serum Albumin Binding of Per- and Polyfluoroalkyl Substances from Five Structural Classes
Authors: Starnes Hannah M. , Jackson Thomas W. , Rock Kylie D. , Belcher Scott M. 
Published: November 2023

AbstractPer- and polyfluoroalkyl substances (PFAS) are a class of over 8,000 chemicals that are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput,in vitrodifferential scanning fluorimetry assay for determination of relative binding affinities of human serum albumin for 24 PFAS congeners from 6 chemical classes. In the current study, we used this differential scanning fluorimetry assay to comparatively examine differences in human, bovine, porcine, and rat serum albumin binding of 8 structurally informative PFAS congeners from 5 chemical classes. With the exception of the fluorotelomer alcohol 1H,1H,2H,2H-perfluorooctanol (6:2 FTOH), each PFAS congener bound by human serum albumin was also bound by bovine, porcine, and rat serum albumin. The critical role of the charged functional headgroup in albumin binding was supported by the inability of serum albumin of each species tested to bind 6:2 FTOH. Significant interspecies differences in serum albumin binding affinities were identified for each of the bound PFAS congeners. Relative to human albumin, perfluoroalkyl carboxylic and sulfonic acids were bound with greater affinity by porcine and rat serum albumin, and perfluoroalkyl ether congeners bound with lower affinity to porcine and bovine serum albumin. These comparative affinity data for PFAS binding by serum albumin from human, experimental model and livestock species reduce critical interspecies uncertainty and improve accuracy of predictive toxicity assessments for PFAS.
Dynamic co-expression modular network analysis of bHLH transcription factors regulation in the potato spindle tuber viroid-tomato pathosystem
Authors: Aviña-Padilla Katia , Zambada-Moreno Octavio , Jimenez-Limas Marco A. , Hammond Rosemarie W. , Hernández-Rosales Maribel 
Published: November 2023

AbstractViroids, minimalist plant pathogens, present significant threats to crops by causing severe diseases. The use of high-throughput sequencing technologies for analyzing the transcriptomes of viroid-infected host plants has yielded informative information on gene regulation by these pathogens, however a complete understanding of the transcriptome data suffers from the inclusion of numerous genes of unknown function. Co-expression analysis addresses this by clustering genes into modules based on global gene expression levels. Our previous study emphasized basic helix-loop-helix protein (bHLH) transcriptional reprogramming in tomato in response to different potato spindle tuber viroid (PSTVd) strains. In the current research, we delve into tissue-specific gene modules, particularly in root and leaf tissues, governed by bHLH transcription factors during PSTVd infections. Utilizing public datasets that span Control (C; (mock-inoculated), PSTVd-mild (M), and PSTVd-severe (S23) strains in time-course infections, we uncovered differentially expressed gene modules. These modules were functionally characterized, identifying essential hub genes. We identified the roles of bHLH transcription factors (TFs) in managing processes like photosynthesis and rapid membrane repair in infected roots. In leaves, external layer alterations influenced photosynthesis, linking bHLH TFs to distinct metabolic functions. Expanding on these findings, we explored bipartite networks, discerning both common and unique bHLH TF regulatory roles, notably highlighting the bifan motif’s significance in these interactions. Through this holistic approach, we deepen our understanding of viroid-host interactions and the intricate regulatory mechanisms underpinning them.
Acetylcholine Promotes Directionally Biased Glutamatergic Retinal Waves
Authors: Zhang Kathy , Su Ashley , Wang Yixiang , Crair Michael 
Published: November 2023

AbstractSpontaneous retinal waves are a critical driving force for the self-organization of the mouse visual system prior to eye-opening. Classically characterized as taking place in three distinct stages defined by their primary excitatory drive, Stage II waves during the first postnatal week are propagated through the volume transmission of acetylcholine while Stage III retinal waves during the second postnatal week depend on glutamatergic transmission from bipolar cells. However, both late Stage II and early Stage III retinal waves share a defining propagation bias toward the temporal-to-nasal direction despite developmental changes in the underlying cholinergic and glutamatergic retinal networks. Here, we leverage genetic and pharmacological manipulations to investigate the relationship between cholinergic and glutamatergic neurotransmission during the transition between Stage II and Stage III wavesin vivo.We find that the cholinergic network continues to play a vital role in the propagation of waves during Stage III after the primary mode of neurotransmission changes to glutamate. In the absence of glutamatergic waves, compensatory cholinergic activity persists but lacks the propagation bias typically observed in Stage III waves. In the absence of cholinergic waves, gap junction-mediated activity typically associated with Stage I waves persists throughout the developmental window in which Stage III waves usually emerge and lacks the spatiotemporal profile of normal Stage III waves, including a temporal-to-nasal propagation bias. Finally, we show that cholinergic signaling through β2 subunit-containing nicotinic acetylcholine receptors, essential for Stage II wave propagation, is also critical for Stage III wave directionality.
GO2Sum: Generating Human Readable Functional Summary of Proteins from GO Terms
Authors: Giri Swagarika Jaharlal , Ibtehaz Nabil , Kihara Daisuke 
Published: November 2023

AbstractUnderstanding the biological functions of proteins is of fundamental importance in modern biology. To represent function of proteins, Gene Ontology (GO), a controlled vocabulary, is frequently used, because it is easy to handle by computer programs avoiding open-ended text interpretation. Particularly, the majority of current protein function prediction methods rely on GO terms. However, the extensive list of GO terms that describe a protein function can pose challenges for biologists when it comes to interpretation. In response to this issue, we developed GO2Sum (Gene Ontology terms Summarizer), a model that takes a set of GO terms as input and generates a human-readable summary using the T5 large language model. GO2Sum was developed by fine-tuning T5 on GO term assignments and free-text function descriptions for UniProt entries, enabling it to recreate function descriptions by concatenating GO term descriptions. Our results demonstrated that GO2Sum significantly outperforms the original T5 model that was trained on the entire web corpus in generating Function, Subunit Structure, and Pathway paragraphs for UniProt entries.
Multiplexed 3D Analysis of Immune States and Niches in Human Tissue
Authors: Yapp Clarence , Nirmal Ajit J. , Zhou Felix , Maliga Zoltan , Tefft Juliann B. , Llopis Paula Montero , Murphy George F. , Lian Christine G. , Danuser Gaudenz , Santagata Sandro , Sorger Peter K. 
Published: November 2023

SUMMARYTissue homeostasis and the emergence of disease are controlled by changes in the proportions of resident and recruited cells, their organization into cellular neighbourhoods, and their interactions with acellular tissue components. Highly multiplexed tissue profiling (spatial omics)1makes it possible to study this microenvironmentin situ, usually in 4-5 micron thick sections (the standard histopathology format)2. Microscopy-based tissue profiling is commonly performed at a resolution sufficient to determine cell types but not to detect subtle morphological features associated with cytoskeletal reorganisation, juxtracrine signalling, or membrane trafficking3. Here we describe a high-resolution 3D imaging approach able to characterize a wide variety of organelles and structures at sub-micron scale while simultaneously quantifying millimetre-scale spatial features. This approach combines cyclic immunofluorescence (CyCIF) imaging4of over 50 markers with confocal microscopy of archival human tissue thick enough (30-40 microns) to fully encompass two or more layers of intact cells. 3D imaging of entire cell volumes substantially improves the accuracy of cell phenotyping and allows cell proximity to be scored using plasma membrane apposition, not just nuclear position. In pre-invasive melanomain situ5, precise phenotyping shows that adjacent melanocytic cells are plastic in state and participate in tightly localised niches of interferon signalling near sites of initial invasion into the underlying dermis. In this and metastatic melanoma, mature and precursor T cells engage in an unexpectedly diverse array of juxtracrine and membrane-membrane interactions as well as looser “neighbourhood” associations6whose morphologies reveal functional states. These data provide new insight into the transitions occurring during early tumour formation and immunoediting and demonstrate the potential for phenotyping of tissues at a level of detail previously restricted to cultured cells and organoids.
Interplay between resource dynamics, network structure and spatial propagation of transient explosive synchronization in an adaptively coupled mouse brain network model
Authors: Ranjan Avinash , Gandhi Saurabh R. 
Published: November 2023

AbstractGeneralized epileptic attacks, which exhibit widespread disruption of brain activity, are characterized by recurrent, spontaneous and synchronized bursts of neural activity that self-initiate and self-terminate through critical transitions. Here we utilize the general framework of explosive synchronization (ES) from complex systems science to study the role of network structure and resource dynamics in the generation and propagation of seizures. We show that a combination of resource constraint and adaptive coupling in a Kuramoto network oscillator model can reliably generate seizure-like synchronization activity across different network topologies, including a biologically derived mesoscale mouse brain network. The model, coupled with a novel algorithm for tracking seizure propagation, provides mechanistic insight into the dynamics of transition to the synchronized state and its dependence on resources; and identifies key brain areas that may be involved in the initiation and spatial propagation of the seizure. The model, though minimal, efficiently recapitulates several experimental and theoretical predictions from more complex models, and makes novel experimentally testable predictions.Significance statement / Author SummaryUnderstanding seizure dynamics at the whole-brain level is crucial for controlling abnormal hypersynchronous activity. Currently, complete brain coverage recordings are lacking in both patients and animal models. We employ network science tools to investigate epileptic seizure-like synchronization in a mouse whole brain network, leveraging network structure and supported dynamics as the basis for seizure evolution. Our results align with experimental findings, suggesting that seizure activity initiates in the cortico-thalamic circuit. Importantly, our novel analysis identifies key nodes, primarily in the cortex, driving this hypersynchronous activity. Our findings highlight network structure’s role in shaping seizure dynamics and the techniques developed here could enhance our control of generalized seizures when combined with patient-specific data.
Robust organ size in Arabidopsis is primarily governed by cell growth rather than cell division patterns
Authors: Burda Isabella , Li Chun-Biu , Clark Frances K. , Roeder Adrienne H. K. 
Published: November 2023

AbstractOrgan sizes and shapes are highly reproducible, or robust, within a species and individuals.Arabidopsis thalianasepals, which are the leaf-like organs that enclose flower buds, have consistent size and shape, which indicates robust development. Counterintuitively, variability in cell growth rate over time and between cells facilitates robust development because cumulative cell growth averages to a uniform rate. Here we investigate how sepal morphogenesis is robust to changes in cell division but not robust to changes in cell growth variability. We live image and quantitatively compare the development of sepals with increased or decreased cell division rate (lgomutant andLGOoverexpression, respectively), a mutant with altered cell growth variability (ftsh4), and double mutants combining these. We find that robustness is preserved when cell division rate changes because there is no change in the spatial pattern of growth. Meanwhile when robustness is lost inftsh4mutants, cell growth accumulates unevenly, and cells have disorganized growth directions. Thus, we demonstratein vivothat both cell growth rate and direction average in robust development, preserving robustness despite changes in cell division.Summary statementRobust sepal development is preserved despite changes in cell division rate and is characterized by spatiotemporal averaging of heterogeneity in cell growth rate and direction.
Impact of body image on the kinematics of gait initiation
Authors: Oku Kyosuke , Tanaka Shinsuke , Nishizaki Yukiko , Fukada Chie , Kida Noriyuki 
Published: November 2023

AbstractIn our daily lives, we walk naturally because we can consider our physical characteristics and formulate appropriate motor plans. However, the impact of changes in body image during motor planning on walking movements remains poorly understood. Therefore, in this study, we investigated how walking movements change when body image is altered. We included 26 participants (13 males, 13 females, aged 18.27±0.52) to perform walking movements under five conditions: open eyes (baseline), closed eyes, closed eyes while imagining their bodies becoming large, closed eyes again, and open eyes again. As a result, under the condition where participants imagined their bodies becoming large, their stride length, step completion time, and foot lift height increased. These results are attributed to the disparity between actual body size and body image, which affects motor planning. The results of this study have potential applications in rehabilitation and sports coaching settings.
Unraveling activation-related rearrangements and intrinsic divergence from ligand-induced conformational changes of the dopamine D3 and D2 receptors
Authors: Lee Kuo Hao , Shi Lei 
Published: November 2023

AbstractEffective rational drug discovery targeting a specific protein hinges on understanding their functional states and distinguishing it from homologs. However, for the G protein coupled receptors, both the activation-related conformational changes (ACCs) and the intrinsic divergence among receptors can be misled or obscured by ligand-induced conformational changes (LCCs). Here, we unraveled ACCs and intrinsic divergence from LCCs of the dopamine D3 and D2 receptors (D3R and D2R), by analyzing their experimentally determined structures and the molecular dynamics simulation results of the receptors bound with different ligands. In addition to the ACCs common to other aminergic receptors, we revealed unique ACCs for these two receptors including TM5e and TM6e shifting away from TM2e and TM3e, with a subtle rotation of TM5e. In identifying intrinsic divergence, we found pronounced outward tilting of TM6e in the D2R compared to the D3R in both experimental structures and simulations with ligands in different scaffolds. This tilting was drastically reduced in the simulations of the receptors bound with nonselective full agonist quinpirole, suggesting a misleading impact of LCCs. Further, in the quinpirole-bound simulations, TM1 showed a greater disparity between these receptors, indicating that LCCs may obscure intrinsic divergence. In addition, our analysis showed that the impact of the nonconserved TM1 propagated to conserved Trp7.40and Glu2.65, both are ligand binding residues. We also found that the D2R exhibited heightened flexibility compared to the D3R in the extracellular portions of TMs 5, 6, and 7, potentially associated with its greater ligand binding site plasticity. Our results lay the groundwork for crafting ligands specifically targeting D2R or D3R with more precise pharmacological profiles.
Joint representation and visualization of derailed cell states with Decipher
Authors: Nazaret Achille , Fan Joy Linyue , Lavallée Vincent-Philippe , Burdziak Cassandra , Cornish Andrew E. , Kiseliovas Vaidotas , Bowman Robert L. , Masilionis Ignas , Chun Jaeyoung , Eisman Shira E. , Wang James , Hong Justin , Shi Lingting , Levine Ross L. , Mazutis Linas , Blei David , Pe’er Dana , Azizi Elham 
Published: November 2023

ABSTRACTBiological insights often depend on comparing conditions such as disease and health, yet we lack effective computational tools for integrating single-cell genomics data across conditions or characterizing transitions from normal to deviant cell states. Here, we present Decipher, a deep generative model that characterizes derailed cell-state trajectories. Decipher jointly models and visualizes gene expression and cell state from normal and perturbed single-cell RNA-seq data, revealing shared and disrupted dynamics. We demonstrate its superior performance across diverse contexts, including in pancreatitis with oncogene mutation, acute myeloid leukemia, and gastric cancer.
GexMolGen: Cross-modal Generation of Hit-like Molecules via Large Language Model Encoding of Gene Expression Signatures
Authors: Cheng Jiabei , Pan Xiaoyong , Fang Yi , Yang Kaiyuan , Xue Yiming , Yan Qingran , Yuan Ye 
Published: November 2023

AbstractDesigning de novo molecules with specific biological activity is an essential task since it holds the potential to bypass the exploration of target genes, which is an initial step in the modern drug discovery paradigm. However, traditional methods mainly screen molecules by comparing the desired molecular effects within the documented experimental results. The data set limits this process, and it is hard to conduct direct cross-modal comparisons. Therefore, we propose a solution based on cross-modal generation called GexMolGen (Gene Expression-based Molecule Generator), which generates hit-like molecules using gene expression signatures alone. These signatures are calculated by inputting control and desired gene expression states. Our model GexMolGen adopts a “first-align-then-generate” strategy, aligning the gene expression signatures and molecules within a mapping space, ensuring a smooth cross-modal transition. The transformed molecular embeddings are then decoded into molecular graphs. In addition, we employ an advanced single-cell large language model for input flexibility and pre-train a scaffold-based molecular model to ensure that all generated molecules are 100% valid. Empirical results show that our model can produce molecules highly similar to known references, whether feeding in- or out-of-domain transcriptome data. Furthermore, it can also serve as a reliable tool for cross-modal screening.
Control of a gene transfer agent cluster inCaulobacter crescentusby transcriptional activation and anti-termination
Authors: Tran Ngat T. , Le Tung B.K. 
Published: November 2023

ABSTRACTGene Transfer Agents (GTAs) are domesticated prophages that cannot self-multiply and be infectious but might have been co-opted to perform biological functions for the host bacteria.Caulobacter crescentus, a bacterium best known as a model organism to study bacterial cell biology and cell cycle regulation, has recently been demonstrated to producebona fideGTA particles (CcGTA). Two direct activators of the CcGTA biosynthetic gene cluster, GafY and GafZ, have been identified, however, it is unknown how GafYZ controls transcription mechanistically or how they coordinate gene expression of the CcGTA gene cluster with other accessory genes elsewhere on the genome for complete CcGTA production. Here, we show that the CcGTA gene cluster is transcriptionally co-activated by GafY, integration host factor (IHF), and by GafZ-mediated transcription anti-termination. We present evidence that GafZ is a novel transcription anti-terminator that likely forms an anti-termination complex with RNA polymerase, NusA, NusG, and NusE to bypass transcription terminators within the 14 kb CcGTA cluster. Overall, we reveal a two-tier regulation that coordinates the synthesis of GTA particles inC. crescentus.