bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contrasting flowering-time among coffee genotypes is associated with ectopic and differential expressions of genes related to environment, floral development, and hormonal regulation
Authors: López Marlon Enrique , Oliveira Raphael Ricon de , Azevedo Lillian Magalhães , Santos Iasminy Silva , Ribeiro Thales Henrique Cherubino , Zhang Dapeng , Chalfun-Junior Antonio 
Published: August 2024

ABSTRACTThe molecular pathways underlying floral activation and development are well described in model species, but exhibit significant diversity in plants that is poorly understood in crops with complex cycles, such asCoffea arabicaL. The reproductive development of coffee plants is biannual, and the flowering time is crucial for the coffee productivity and cup quality. In this study, we explored the plasticity of floral development and flowering-time of contrasting coffee genotypes to understand the associated metabolic and regulatory transcriptional profiles. Firstly, we compared the reproductive development of three coffee genotypes, confirming thatAcauãis late flowering,Oeirasis early flowering, and the natural mutantSemperflorens(Sf) exhibits continuous flowering throughout the year. Analysis of sugar and ethylene content revealed quantitative differences between genotypes in both leaves and floral buds. To associate these phenotypic differences with the regulatory developmental pathways, we performed RNA-seq analysis comparing the shoot apical meristems, floral buds and leaves of different genotypes. Our analysis identified 12.478 differentially expressed genes, which showed enriched terms mainly related to hormonal regulation, external stimulus and floral development. Notably, some major players of reproductive development, as homologs ofFLOWERING LOCUS Tand MADS-box genes, showed contrasting expression patterns, generally being ectopically upregulated in theSfmutant. These findings were associated with the phenotypic differences among coffee genotypes. In conclusion, the present study improves the understanding of the divergence of floral development in coffee, providing valuable insights for directing breeding programs and future studies aiming at controlling floral development and enhancing crop production.
Probabilistic modeling reveals coordinated social interaction states and their multisensory bases
Authors: Stednitz Sarah Josephine , Lesak Andrew , Fecker Adeline L , Painter Peregrine , Washbourne Phil , Mazzucato Luca , Scott Ethan K 
Published: August 2024

ABSTRACTSocial behavior across animal species ranges from simple pairwise interactions to thousands of individuals coordinating goal-directed movements. Regardless of the scale, these interactions are governed by the interplay between multimodal sensory information and the internal state of each animal. Here, we investigate how animals use multiple sensory modalities to guide social behavior in the highly social zebrafish (Danio rerio) and uncover the complex features of pairwise interactions early in development. To identify distinct behaviors and understand how they vary over time, we developed a new hidden Markov model with constrained linear-model emissions to automatically classify states of coordinated interaction, using the movements of one animal to predict those of another. We discovered that social behaviors alternate between two interaction states within a single experimental session, distinguished by unique movements and timescales. Long-range interactions, akin to shoaling, rely on vision, while mechanosensation underlies rapid synchronized movements and parallel swimming, precursors of schooling. Altogether, we observe spontaneous interactions in pairs of fish, develop novel hidden Markov modeling to reveal two fundamental interaction modes, and identify the sensory systems involved in each. Our modeling approach to pairwise social interactions has broad applicability to a wide variety of naturalistic behaviors and species and solves the challenge of detecting transient couplings between quasi-periodic time series.HIGHLIGHTSZebrafish exhibit distinct correlated interaction states with unique timescales.Delayed interactions are visual while synchronization requires mechanosensation.A new class of hidden Markov model segments social interactions into discrete states.States alternate within a session, revealing real-time dynamics of social behavior.
Mechano-adaptation: Exercise-driven Piezo1 & Piezo2 augmentation and chondroprotection in articular cartilage
Authors: Jing Xingyu , Kotelsky Alexander , Zhang Yaxin , Dirksen Robert , Mannava Sandeep , Buckley Mark , Lee Whasil 
Published: August 2024

AbstractChondrocytes in adult joints are mechanosensitive post-mitotic quiescent cells with robustly expressed both Piezo1 and Piezo2 ion channels. Here, we examined the mechano-adaptation and Piezo modulations in articular chondrocytes using a mouse exercise model. We first found differential expression patterns of PIEZO1 and PIEZO2 in articular chondrocytes of healthy knee joints; chondrocytes in tibial cartilage (T) exhibit significantly higher PIEZO1 and PIEZO2 than femoral chondrocytes (F). Interestingly, a few weeks of exercise caused both PIEZO1 and PIEZO2 augmentation in F and T compared to the sedentary control group. Despite the increased expression levels of these mechanosensors, chondrocytes in exercised cartilage exhibit significantly reduced mechanical susceptibility against 1mJ impact. PIEZO1 modulation was relatively more rapid than PIEZO2 channels post-exercise. We tested the exercise-induced effect using Piezo1-conditional knockout (Pz1-cKO; Agc1CreERT2;Piezo1fl/fl). Pz1-cKO mice exhibit diminished exercise-driven chondroprotection against 1mJ impact, suggesting essential roles of Piezo1-mediated mechanotransduction for physiologic-induced cartilage matrix homeostasis. In addition, using a mouse OA model, we further found the modulated PIEZO1 in chondrocytes, consistent with reports in Ren et al., but without PIEZO2 modulations over OA progression. In summary, our data reveal the distinctly tuned Piezo1 and Piezo2 channels in chondrocytes post-exercise and post-injury, in turn modulating the mechanical susceptibility of chondrocytes. We postulate that Piezo1 is a tightly-regulatedbiphasic biomarker; Piezo1 antagonism may increase cellular survival post-injury and Piezo1 (with Piezo2) agonism to promote cartilage ECM restoration.
An Information Theory Framework for Movement Path Segmentation and Analysis
Authors: Sethi Varun , Spiegel Orr , Salter Richard , Cain Shlomo , Toledo Sivan , Getz Wayne M. 
Published: August 2024

AbstractImproved animal tracking technologies provide opportunities for novel segmentation of movement tracks/paths into behavioral activity modes (BAMs) critical to understanding the ecology of individuals and the functioning of ecosystems. Current BAM segmentation includes biological change point analyses and hidden Markov models. Here we use an elemental approach to segmenting tracks intoµ-step-long “base segments” andm-base-segment-long “words.” These are respectively clustered intonstatistical movement elements (StaMEs) andk“raw” canonical activity modes (CAMs). Once the words are coded usingmextracted StaME symbols, those encoded by the same string of symbols, after a rectification processes has been implemented to minimize misassigned words, are identified with particular “rectified” CAM types. The percent of reassignment errors, along with information theory measures, are used to compare the efficiencies of coding both simulated and empirical barn owl data for a selection of parameter values and approaches to clustering.
VR HMD color calibration and accurate control of emitted light using Three.js
Authors: Duay Killian , Mizokami Yoko , Nagai Takehiro 
Published: August 2024

AbstractVirtual Reality (VR) can be used to design and create new types of psychophysical experiments. Its main advantage is that it frees us from the physical limitations of real-life experiments and the hardware and software limitations of experiments running on 2D displays and computer graphics. However, color calibration of the displays is often required in vision science studies. Recent studies have shown that a standard color calibration of a Head-Mounted Display (HMD) can be very challenging and comes with significant drawbacks. In this paper, we introduce a new approach that allows for successful color calibration of an HMD and overcomes the disadvantages associated with other solutions. We utilize a new VR engine, Three.js, which offers several advantages. This paper details our setup and methodology, and provides all the elements required to reproduce the method, including the source code. We also apply our method to evaluate and compare three different HMDs: HTC Vive Pro Eye, Meta Quest Pro, and Meta Quest 3. The results show that the HTC Vive Pro Eye performs excellently, the Meta Quest Pro performs well, and the Meta Quest 3 performs poorly.
Integration of immune cell-target cell conjugate dynamics changes the time scale of immune control of cancer
Authors: Yang Qianci , Traulsen Arne , Altrock Philipp 
Published: August 2024

AbstractThe human immune system can recognize, attack, and eliminate cancer cells, but cancers can escape this immune surveillance. The dynamics of these cancer control mechanisms by cells of the adaptive immune system can be captured by variants of ecological predator-prey models. These dynamical systems can describe the interaction of cancer cells and, e.g., effector T cells to form tumor cell-immune cell conjugates, cancer cell killing, immune cell activation, and T cell exhaustion. Target (tumor) cell-T cell conjugation is integral to the adaptive immune system’s cancer control or immunotherapy dynamics. However, it is incompletely understood whether conjugate dynamics should be explicitly included in mathematical models of cancer-immune interactions. Here, we analyze the dynamics of a cancer-effector T cell system regarding the impact of explicitly modeling the conjugate compartment to elucidate the role of cellular conjugate dynamics. We formulate a deterministic modeling framework to compare possible equilibria and their stability, such as tumor extinction, tumor-immune coexistence (tumor control), or tumor escape. We also formulate the stochastic analog of this system to analyze the impact of demographic fluctuations that arise when cell populations are small. We find that explicit consideration of a conjugate compartment can change long-term steady-state, critically change the time to reach an equilibrium, alter the probability of tumor escape, and lead to very different extinction time distributions. Thus, we demonstrate the importance of the conjugate compartment in defining tumor-effector interactions. Accounting for transitionary compartments of cellular interactions may better capture the dynamics of tumor control and progression.
Knockout of the tomatoHAIRY MERISTEM 4alters phloem-characteristics and impairs development
Authors: Khedia Jackson , Vishwakarma Abhay Pratap , Galsurker Ortal , Corem Shira , Gupta Suresh Kumar , Arazi Tzahi 
Published: August 2024

AbstractThe HAIRY MERISTEM (HAM) gene family encodes Type I and II GRAS domain transcription factors in plants. Type II HAMs, predominantly expressed in meristems and regulated by microRNA171, are essential for maintaining undifferentiated meristems, a role conserved across various species. Conversely, the functions of Type I HAMs have been less characterized. In this study, we investigated the role of SlHAM4, a Type I HAM in tomato. Using publicly available expression data and a GUS reporter gene driven by the nativeSlHAM4promoter, we determined thatSlHAM4is predominantly expressed in phloem tissues. CRISPR-inducedSlHAM4loss-of- function mutations (slham4CR) resulted in a range of shoot and fruit abnormalities, which were fully reversed by reintroducingSlHAM4under its native promoter in the mutant background. Mutant abnormalities included increased anthocyanin pigmentation in the leaf and sepal primordia, reminiscent of the phenotypes observed in certain Arabidopsis mutants with compromised phloem, and development of simpler leaves, which was associated with reduction in external phloem area in the leaf rachis. In addition,slham4CRplants produced significantly smaller fruits of which a fraction of them exhibited catface-like scars, attributed to tears which occurred in the pericarp of mutant ovaries following fruit set. Transcriptome analysis of the wild-type looking mutant ovaries at anthesis revealed specific downregulation of genes implicated in phloem development and functions, in particular those expressed in companion cells (CC). We propose that SlHAM4 is necessary for proper phloem function in part by regulating the expression of a suite of CCs genes that encode essential phloem proteins.One-sentence summarySlHAM4is predominantly expressed in the phloem and its knockout alters phloem- characteristics and impair development highlighting its requirement for proper phloem functionality.
Integrated Single-Cell Multiomic Profiling of Caudate Nucleus Suggests Key Mechanisms in Alcohol Use Disorder
Authors: Green Nick , Gao Hongyu , Chu Xiaona , Yuan Qiuyue , McGuire Patrick , Lai Dongbing , Jiang Guanglong , Xuei Xiaoling , Reiter Jill L. , Stevens Julia , Sutherland Greg T. , Goate Alison M. , Pang Zhiping P. , Slesinger Paul A. , Hart Ronald P. , Tischfield Jay A. , Agrawal Arpana , Wang Yue , Duren Zhana , Edenberg Howard J. , Liu Yunlong 
Published: August 2024

AbstractAlcohol use disorder (AUD) induces complex transcriptional and regulatory changes across multiple brain regions including the caudate nucleus, which remains understudied. Using paired single-nucleus RNA-seq and ATAC-seq on caudate samples from 143 human postmortem brains, including 74 with AUD, we identified 17 distinct cell types. We found that a significant portion of the alcohol-induced changes in gene expression occurred through altered chromatin accessibility. Notably, we identified novel transcriptional and chromatin accessibility differences in medium spiny neurons, impacting pathways such as RNA metabolism and immune response. A small cluster of D1/D2 hybrid neurons showed distinct differences, suggesting a unique role in AUD. Microglia exhibited distinct activation states deviating from classical M1/M2 designations, and astrocytes entered a reactive state partially regulated byJUND, affecting glutamatergic synapse pathways. Oligodendrocyte dysregulation, driven in part byOLIG2, was linked to demyelination and increased TGF-β1 signaling from microglia and astrocytes. We also observed increased microglia-astrocyte communication via the IL-1β pathway. Leveraging our multiomic data, we performed cell type-specific expression quantitative trait loci analysis, integrating that with public genome-wide association studies to identify AUD risk genes such asADALandPPP2R3C, providing a direct link between genetic variants, chromatin accessibility, and gene expression in AUD. These findings not only provide new insights into the genetic and cellular mechanisms in the caudate related to AUD but also demonstrate the broader utility of large-scale multiomic studies in uncovering complex gene regulation across diverse cell types, which has implications beyond the substance use field.
Expanding the scope of a catalogue search to bioisosteric fragment merges using a graph database approach
Authors: Wills Stephanie , Sanchez-Garcia Ruben , Roughley Stephen D. , Merritt Andy , Hubbard Roderick E. , von Delft Frank , Deane Charlotte M. 
Published: August 2024

AbstractThe efficiency of fragment-to-lead optimization could be improved by automated workflows for the design of follow-up compounds. Pipelines that are able to fully exploit the interaction opportunities identified from the crystal structures of bound fragments would greatly aid this goal. To do so, these pipelines need to require minimal intervention from the user and be computationally efficient. In this work, we describe an updated version of our fragment merging methodology, which provides several feature enhancements, primarily by expanding the chemical space searched, allowing the identification of more diverse follow-up compounds, thus maximizing the chances of finding successful hits. While the original method focused on finding ‘perfect merges’, meaning compounds that directly incorporate substructures from the original fragments, here we expand the search to what we term ‘bioisosteric merges’, involving the incorporation of substructures that replicate the pharmacophoric features of the original fragments but may not be exactly identical. Unlike existing pharmacophore and shape-based descriptors used for virtual screening, this approach combines the search for these properties with the incorporation of novelty, which is necessary when searching for ways to link together distinct substructures. Compared with ‘perfect merging’, our new approach is able to find compounds that are directly informed by structures within the original fragments but are more chemically diverse. We contrast our approach with the use of a pharmacophore-constrained docking pipeline, run in parallel for select fragment pairs, and show that our method requires between 1.1-45.9-fold less computational time for conformer generation per merging ‘hit’ identified, referring to compounds that show a favourable degree of shape and colour overlap and recapitulation of original fragment interactions. Overall, our results show that our method has potential to be used to generate designs inspired by all fragments within a given pocket.
Spatiotemporal Characterization of Cyclooxygenase Pathway Enzymes During Vertebrate Embryonic Development
Authors: Leathers Tess A. , Ramarapu Raneesh , Rogers Crystal D. 
Published: August 2024

AbstractVertebrate development is regulated by several complex well-characterized morphogen signaling pathways, transcription factors, and structural proteins, but less is known about the enzymatic pathways that regulate early development. We have identified that factors from the inflammation-mediating cyclooxygenase (COX) signaling pathway are expressed at early stages of development in avian embryos. UsingGallus gallus(chicken) as a research model, we characterized the spatiotemporal expression of a subset of genes and proteins in the COX pathway during early neural development stages. Specifically, here we show expression patterns of COX1, COX2, and microsomal prostaglandin E synthase-2 (mPGES-2) as well as the genes encoding these enzymes. Unique expression patterns of individual players within the COX pathway suggest that they may play non-canonical/non-traditional roles in the embryo compared to their roles in the adult. Future work should examine the function of the COX pathway in tissue specification and morphogenesis and determine if these expression patterns are conserved across species.Abstract FigureGraphical abstract.Spatiotemporal characterization of cyclooxygenase pathway enzymes during vertebrate embryonic development.
Differential Expression Analysis for Spatially Correlated Data
Authors: Vasconcelos Ana Gabriela , McGuire Daniel , Simon Noah , Danaher Patrick , Shojaie Ali 
Published: August 2024

AbstractDifferential expression is a key application of imaging spatial transcriptomics, moving analysis beyond cell type localization to examining cell state responses to microenvironments. However, spatial data poses new challenges to differential expression: segmentation errors cause bias in fold-change estimates, and correlation among neighboring cells leads standard models to inflate statistical significance. We find that ignoring these issues can result in considerable false discoveries that greatly outnumber true findings. We present a suite of solutions to these fundamental challenges, and implement them in the R package smiDE. spatial transcriptomics, differential expression, segmentation error mitigation, spatial correlation, spatial random effects model
The interplay between motor cost and self-efficacy related to walking across terrain in gaze and walking decisions
Authors: da Eira Silva Vinicius , Marigold Daniel S. 
Published: August 2024

ABSTRACTMovement-related decisions, such as where to step and which path to take, happen throughout each day. Shifts in gaze serve to extract task-relevant information necessary to make these decisions. We are only beginning to appreciate the factors that affect this information-seeking gaze behaviour. Here, we aimed to determine how a person’s belief in their ability to perform an action (i.e., self-efficacy) affected gaze and path choice when choosing between walking paths with different terrains and/or lengths (reflecting different energetic costs). We demonstrated that, when manipulated separately (i.e., paths had different lengths or different terrains), participants looked longer and more frequently and chose the paths with either less expected energetic cost or those for which they had a higher self-efficacy rating. When encountering environments where paths differed in both length and terrain, participants directed gaze progressively more to the longer path as the self-efficacy rating of this path increased and the disparity in rating with the shorter (less costly) path grew; they also chose the higher-rated path more frequently regardless of path length. These results provide evidence for a contribution of self-efficacy and energetic cost in guiding gaze and walking decisions. Interestingly, self-efficacy beliefs appear to play a more dominant role in both behaviours.
A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding
Authors: Goode Travis D. , Alipio Jason Bondoc , Besnard Antoine , Pathak Devesh , Kritzer-Cheren Michael D. , Chung Ain , Duan Xin , Sahay Amar 
Published: August 2024

SUMMARYAdaptive regulation of feeding depends on linkage of internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation of a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation of underlying cell-types and circuitry is lacking. Here, we identify an evolutionary conserved and discrete Prodynorphin (Pdyn)-expressing subpopulation of Somatostatin (Sst)-expressing inhibitory neurons in the dorsolateral septum (DLS) that receives primarily dorsal, but not ventral, hippocampal inputs. DLS(Pdyn) neurons inhibit LHA GABAergic neurons and confer context- and internal state-dependent calibration of feeding. Viral deletion ofPdynin the DLS mimicked effects seen with optogenetic silencing of DLSPdynINs, suggesting a potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling in contextual regulation of food-seeking. Together, our findings illustrate how the dorsal hippocampus has evolved to recruit an ancient LHA feeding circuit module throughPdynDLS inhibitory neurons to link contextual information with regulation of food consumption.HIGHLIGHTSDLS(Pdyn) neurons receive dense input from the dorsal but not ventral hippocampusDLS(Pdyn) neurons inhibit GABAergic neurons in the LHASilencing dorsal hippocampus-DLS(Pdyn)-LHA circuit nodes abolishes context-conditioned feedingPdynin the DLS is necessary for context-conditioned feeding