bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digitize your Biology! Modeling multicellular systems through interpretable cell behavior
Authors: Johnson Jeanette A.I. , Stein-O’Brien Genevieve L. , Booth Max , Heiland Randy , Kurtoglu Furkan , Bergman Daniel R. , Bucher Elmar , Deshpande Atul , Forjaz André , Getz Michael , Godet Ines , Lyman Melissa , Metzcar John , Mitchell Jacob , Raddatz Andrew , Rocha Heber , Solorzano Jacobo , Sundus Aneequa , Wang Yafei , Gilkes Danielle , Kagohara Luciane T. , Kiemen Ashley L. , Thompson Elizabeth D. , Wirtz Denis , Wu Pei-Hsun , Zaidi Neeha , Zheng Lei , Zimmerman Jacquelyn W. , Jaffee Elizabeth M. , Chang Young Hwan , Coussens Lisa M. , Gray Joe W. , Heiser Laura M. , Fertig Elana J. , Macklin Paul 
Published: September 2023

ABSTRACTCells are fundamental units of life, constantly interacting and evolving as dynamical systems. While recent spatial multi-omics can quantitate individual cells’ characteristics and regulatory programs, forecasting their evolution ultimately requires mathematical modeling. We develop a conceptual framework—a cell behavior hypothesis grammar—that uses natural language statements (cell rules) to create mathematical models. This allows us to systematically integrate biological knowledge and multi-omics data to make them computable. We can then perform virtual “thought experiments” that challenge and extend our understanding of multicellular systems, and ultimately generate new testable hypotheses. In this paper, we motivate and describe the grammar, provide a reference implementation, and demonstrate its potential through a series of examples in tumor biology and immunotherapy. Altogether, this approach provides a bridge between biological, clinical, and systems biology researchers for mathematical modeling of biological systems at scale, allowing the community to extrapolate from single-cell characterization to emergent multicellular behavior.
Multimodal subspace independent vector analysis effectively captures the latent relationships between brain structure and function
Authors: Li Xinhui , Kochunov Peter , Adali Tulay , Silva Rogers F. , Calhoun Vince D. 
Published: September 2023

AbstractA key challenge in neuroscience is to understand the structural and functional relationships of the brain from high-dimensional, multimodal neuroimaging data. While conventional multivariate approaches often simplify statistical assumptions and estimate one-dimensional independent sources shared across modalities, the relationships between true latent sources are likely more complex – statistical dependence may exist within and between modalities, and span one or more dimensions. Here we present Multimodal Subspace Independent Vector Analysis (MSIVA), a methodology to capture both joint and unique vector sources from multiple data modalities by defining both cross-modal and unimodal subspaces with variable dimensions. In particular, MSIVA enables flexible estimation of varying-size independent subspaces within modalities and their one-to-one linkage to corresponding sub-spaces across modalities. As we demonstrate, a main benefit of MSIVA is the ability to capture subject-level variability at the voxel level within independent subspaces, contrasting with the rigidity of traditional methods that share the same independent components across subjects. We compared MSIVA to a unimodal initialization baseline and a multimodal initialization baseline, and evaluated all three approaches with five candidate subspace structures on both synthetic and neuroimaging datasets. We show that MSIVA successfully identified the ground-truth subspace structures in multiple synthetic datasets, while the multimodal baseline failed to detect high-dimensional subspaces. We then demonstrate that MSIVA better detected the latent subspace structure in two large multimodal neuroimaging datasets including structural MRI (sMRI) and functional MRI (fMRI), compared with the unimodal baseline. From subsequent subspace-specific canonical correlation analysis, brain-phenotype prediction, and voxelwise brain-age delta analysis, our findings suggest that the estimated sources from MSIVA with optimal subspace structure are strongly associated with various phenotype variables, including age, sex, schizophrenia, lifestyle factors, and cognitive functions. Further, we identified modality- and group-specific brain regions related to multiple phenotype measures such as age (e.g., cerebellum, precentral gyrus, and cingulate gyrus in sMRI; occipital lobe and superior frontal gyrus in fMRI), sex (e.g., cerebellum in sMRI, frontal lobe in fMRI, and precuneus in both sMRI and fMRI), schizophrenia (e.g., cerebellum, temporal pole, and frontal operculum cortex in sMRI; occipital pole, lingual gyrus, and precuneus in fMRI), shedding light on phenotypic and neuropsychiatric biomarkers of linked brain structure and function.
Dynamics of membrane tubulation coupled with fission by a two-component module revealed on polymer cushioned bilayer islands
Authors: Bhattacharyya Soumya , Pucadyil Thomas J. 
Published: September 2023

SummaryMembrane tubulation coupled with fission (MTCF) is a widespread cellular phenomenon but mechanisms for their coordination remain unclear. This is partly because of the lack of assays to monitor dynamics of membrane tubulation. Using polymer cushioned bilayer islands, we analyze functions of the membrane tubulator Bridging Integrator 1 (BIN1) mixed with the fission catalyst dynamin2 (Dyn2). Our results reveal that this mixture constitutes a minimal two-component module that demonstrates MTCF. MTCF is an emergent property and arises because BIN1 dually functions in facilitating peripheral recruitment while inhibiting membrane binding of Dyn2 in a dose-dependent manner. MTCF is therefore apparent only at high Dyn2 to BIN1 ratios. Because of their mutual involvement in T-tubules biogenesis, mutations in BIN1 and Dyn2 are associated with centronuclear myopathies (CNM) and our analysis links the pathology with aberrant MTCF. Together, our results establish cushioned bilayer islands as a facile template for the quantitative analysis of membrane tubulation and inform of mechanisms that coordinate MTCF.
Decoding genetic architecture of dog complex traits by constructing fine-scale genomic ancestry of admixture
Authors: Zhao Shilei , Wang Guo-Dong , Liu Yanhu , Zhang Ya-Ping , Chen Hua 
Published: September 2023

AbstractDomestic animals and plants exhibit remarkable phenotypic diversity in terms of morphology, behavior, and physiology, which can be attributed to the complex interbreeding process of various breeds and artificial selection. Here we develop a method that can efficiently construct fine-scale interbreeding history of local segments along the genome. Since ancestral breeds usually exhibit diverse phenotypes, the method provides a valuable approach for unraveling the genetic architecture of complex traits in admixed breeds. Simulated data demonstrates that the method performs well, even in scenarios involving complex interbreeding with up to 19 ancestral breeds.The method is applied to analyze three mixed dog breeds, Irish Wolfhound, Giant Schnauzer, and Miniature Schnauzer, representing instances of body-size enlargement and miniaturization. Numerous novel ancestor breed-specific genes determining body size are identified, includingFGFR2, WDR11, andFARS2. We also validate genes reported in previous GWAS or genomic sweep scans, such asLCORL, STC2, NPR2, andFGF4. These findings highlight the validity of the method as a valuable tool for investigating the genetic basis underlying ancestry-specific traits in domestic animals and plants with complex interbreeding histories.
Motivation upregulates the adaptive response in sensorimotor learning
Authors: Khatib Salma , Chib Vikram S. , Mawase Firas 
Published: September 2023

AbstractMotivational state plays a critical role in our ability to learn new motor skills; however, the mechanisms by which motivation influences motor learning are poorly understood. Using a motor learning paradigm in which motivation was varied in a trial-by-trial manner, we found that motivation affects learning by upregulating the rate of the adaptive response, increasing individuals’ speed of learning. This unveils previously unidentified evidence for a mechanism through which motivation shapes error-based motor learning.
Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS
Authors: Montañana-Rosell Roser , Selvan Raghavendra , Hernández-Varas Pablo , Kaminski Jan M. , Ahlmark Dana B. , Kiehn Ole , Allodi Ilary 
Published: September 2023

AbstractAmyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons. Major focus has been directed to motor neuron intrinsic properties as a cause for degeneration while less attention has been given to the contribution of spinal interneurons. In the present work, we applied multiplexing detection of transcripts and machine learning-based image analysis to investigate the fate of multiple spinal interneuron populations during ALS progression in the SOD1G93Amouse model. The analysis showed that spinal inhibitory interneurons are affected early in disease, before motor neurons death, and are characterized by a slow progressive degeneration, while excitatory interneurons are affected later with a steep progression. Moreover, we report differential vulnerability within inhibitory and excitatory subpopulations, with interneurons directly projecting onto motor neurons being preferentially affected. Our study reveals a strong interneuron involvement in ALS development with interneuron specific degeneration. This points to differential involvement of diverse spinal neuronal circuits that eventually may be determining for motor neuron degeneration.TeaserA new approach to study the motor neuron disorder Amyotrophic Lateral Sclerosis shows the early and differential dysregulation of spinal interneurons.
A Novel Fluorogenic Spin Probe for Real-time Monitoring of Mitochondrial Reactive Oxygen Species (mROS) Generation in anin vitroStroke Model
Authors: Hou Shanshan , Bi Yue , Li Chunyan , Shan Zhiying , Bi Lanrong 
Published: September 2023

ABSTRACTThe extent of oxidative damage caused by a stroke can be assessed by monitoring mitochondrial reactive oxygen species (mROS), which can further aid in early diagnosis and evaluation of treatment efficacy. Mitochondrial ROS have been identified as a potential biomarker for stroke, as they are known to cause oxidative stress and mitochondrial dysfunction in brain tissue. However, monitoring reversible mROS levels has been challenging due to the lack of appropriate probes. In this study, we developed a fluorogenic spin probe, Mito-RT-ROS, based on the rhodamine skeleton, which demonstrated good sensitivity for reversible monitoring of mROS in a physiological environment such as starvation and recovery. We also evaluated the probe’s efficacy in anin vitrostroke model for real-time tracking of mROS generation in a pathological setting.
CaMKIIa+ neurons in the bed nucleus of the stria terminalis modulate pace of natural reward seeking depending on internal state
Authors: Huijgens Patty T. , Heijkoop Roy , Vanderschuren Louk J.M.J. , Lesscher Heidi M.B. , Snoeren Eelke M.S. 
Published: September 2023

AbstractThis study aims to investigate the underlying neurobiological mechanisms that regulate natural reward seeking behaviors, specifically in the context of sexual behavior and sucrose self-administration. The role of CaMKIIa+ neurons in the bed nucleus of the stria terminalis (BNST) was explored using chemogenetic silencing and -stimulation. Additionally, the study examined how these effects interacted with the internal state of the animals. Through detailed behavioral analysis, it was demonstrated that CaMKIIa+ neurons in the BNST play a significant role in the regulation of both sexual behavior and sucrose self-administration. Although the behavioral outcome measures differed between the two behaviors, the regulatory role of the CaMKIIa+ neurons in the BNST was found to converge on the modulation of the pacing of engagement in these behaviors in male rats. Moreover, our study confirmed that the internal physiological state of the animal affects how the BNST modulates these behaviors. These findings suggest that different types of natural rewards may recruit a similar brain circuitry to regulate the display of motivated behaviors. Overall, this research provides valuable insights into the neural mechanisms underlying natural reward seeking and sheds light on the interconnected nature of reward-related behaviors in male rats.Abstract Figure
Inferring inter-chromosomal rearrangements and ancestral linkage groups from synteny
Authors: Mackintosh Alexander , de la Rosa Pablo Manuel Gonzalez , Martin Simon H. , Lohse Konrad , Laetsch Dominik R. 
Published: September 2023

AbstractChromosome rearrangements shape the structure of the genome and influence evolutionary processes. Inferring ancestral chromosomes and rearrangements across a phylogenetic tree is therefore an important analysis within evolutionary genetics. One approach to this inference problem is to focus on synteny information, i.e. the co-occurrence of loci on the same chromosome. Although algorithms for inferring ancestral linkage groups (ALGs) and inter-chromosomal rearrangements from synteny have been previously described, they have seldom been applied to modern genome data. Here we implement these algorithms in a command-line tool,syngraph, and evaluate their performance using simulations that include a mix of different rearrangements and types of error. We show that ALGs and rearrangements can be recovered when the rearrangement frequency per-branch is well below the number of chromosomes. We demonstrate that competing models of rearrangement can be inferred by comparing observed results to simulations. Finally, we reanalyse genome assemblies of rhabditid nematodes and find that independent fusions of the same ALGs pose a challenge that is difficult to overcome without gene-order information. Our simulations and analysis of real data demonstrate both the promise and limitations of using synteny information to infer patterns of genome evolution.
Nucleic Acid Mediated Activation of a Short Prokaryotic Argonaute Immune System
Authors: Kottur Jithesh , Malik Radhika , Aggarwal Aneel K. 
Published: September 2023

AbstractThe continual pressure of invading DNA has led bacteria to develop numerous immune systems, including a short prokaryotic Argonaute (pAgo) TIR-APAZ system (SPARTA) that is activated by invading DNA to unleash its TIR domain for NAD(P)+hydrolysis. To gain a molecular understanding of this activation process, we resolved a crystal structure of SPARTA heterodimer in the absence of guide RNA/target ssDNA at 2.66Å resolution and a cryo-EM structure of the SPARTA oligomer (tetramer of heterodimers) bound to guide RNA/target ssDNA at nominal 3.15-3.35Å resolution. The crystal structure provides a high-resolution view of the TIR-APAZ protein and the MID-PIWI domains of short pAgo - wherein, the APAZ domain emerges as equivalent to the N, L1 and L2 regions of long pAgos and the MID domain has a unique insertion (insert57). A comparison to cryo-EM structure reveals regions of the PIWI (loop10-9) and APAZ (helix αN) domains that reconfigure to relieve auto-inhibition to permit nucleic acid binding and transition to an active oligomer. Oligomerization is accompanied by the nucleation of the TIR domains in a parallel-strands arrangement for catalysis. Together, the structures provide a visualization of SPARTA before and after RNA/ssDNA binding and reveal the basis of SPARTA’s active assembly leading to NAD(P)+degradation and abortive infection.
Metabolic adaptation pilots the differentiation of human hematopoietic cells
Authors: Racine Laëtitia , Parmentier Romuald , Niphadkar Shreyas , Chhun Julie , Martignoles Jean-Alain , Delhommeau François , Laxman Sunil , Paldi Andras 
Published: September 2023

AbstractA continuous supply of energy and metabolic intermediates is an essential prerequisite for survival and the highest priority for the cell. We hypothesize that cell differentiation is a process of optimization of energy flow in a changing environment through phenotypic adaptation. A mechanistic basis of this hypothesis is provided by the established link between core energy metabolism and epigenetic covalent modifications of chromatin. This hypothesis predicts that early metabolic perturbations impact subsequent differentiation. To test this, we induced transient metabolic perturbations in undifferentiated human hematopoietic cells using pharmacological inhibitors targeting key metabolic reactions. We recorded changes in chromatin structure and gene expression, as well as phenotypic alterations by single-cell ATAC and RNA sequencing, time-lapse microscopy and flow cytometry. Our observations suggest that these metabolic perturbations are shortly followed by alterations in chromatin structure, leading to changes in gene expression. We also show that these transient fluctuations alter the differentiation potential of the cells.
Flatworm transcriptomes reveal widespread parasitism by histophagous ciliates
Authors: Woodcock M. Ryan , Powers Kaleigh , Snead Kirsten , Pellettieri Jason 
Published: September 2023

AbstractUnicellular ciliates likeTetrahymenaare best known as free-living bacteriovores, but many species are facultative or obligate parasites. These ‘histophages’ feed on the tissues of hosts ranging from planarian flatworms to commercially important fish and the larvae of imperiled freshwater mussels. Here, we developed a novel bioinformatics pipeline incorporating the nonstandard ciliate genetic code and used it to search for Ciliophora sequences in 34 publicly available Platyhelminthes EST libraries. From 2,615,036 screened ESTs, we identified nearly 6,000 high-confidence ciliate transcripts, supporting parasitism of seven additional flatworm species. We also cultured and identifiedTetrahymenafrom nine terrestrial and freshwater planarians, including invasive earthworm predators from the genusBipaliumand the widely studied regeneration modelsDugesia japonicaandSchmidtea mediterranea. A cophylogenetic reconstruction provides strong evidence for coevolution of histophagous Ciliophora with their Platyhelminthes hosts. We further report the antiprotozoal aminoglycoside paromomycin expelsTetrahymenafromS. mediterranea, providing new opportunities to investigate the effects of this relationship on planarian biology. Together, our findings raise the possibility that invasive flatworms constitute a novel dispersal mechanism forTetrahymenaparasites and position the Platyhelminthes as an ideal model phylum for studying the ecology and evolution of histophagous ciliates.
Synaptic tagging and capture underlie neuronal co-allocation and temporal association memory in behaving mice
Authors: Sakai Y , Brizard B , Zapata J , Zenelaj X , Tanti A , Camus V , Belzung C , Surget A 
Published: September 2023

ABSTRACTEpisodic memory has the ability to link distinct memories formed at temporal proximity (minutes-hours) into a coherent episodic representation. The neuronal mechanisms supporting such time associations remain however to be understood. The synaptic tagging and capture hypothesis (STC) provides a theoretical framework in which plasticity-related proteins produced for consolidating a memory trace at a synapse can potentially benefit to the consolidation of another trace at another synapse of the same neuron, thereby promoting neuronal co-allocations and temporal associations of memory traces. STC has however never been demonstrated in behaving animals, leaving its existence and functional relevance for memory formation unknown. We therefore investigated STC-like mechanisms in freely-behaving mice by recording hippocampal CA1 neurons during encoding and retrieval of distinct events. We found that reactivation of engram neurons at retrieval and the stability of place cells were strongly impaired by protein synthesis inhibition during encoding, but strikingly, were rescued in neurons that were coactive at another encoding close in time, having potentially benefitted from proteins produced at temporal proximity, as predicted by STC hypothesis. All our results together provide the first evidence of STC-like mechanisms in behaving animals and reveal an instrumental role of STC for time association of memory traces.
Building resilience in early career mental health professionals
Authors: Nelson Rosalyn , Baker Felicity , Burrell Joanna , Hardy Gillian 
Published: September 2023

Purpose
Resilience can protect against workplace stress, benefit psychological wellbeing and promote effective clinical practice in mental health professionals. The purpose of this study was to consider the feasibility and acceptability of resilience training for trainee mental health professionals based on the skills-based model of personal resilience (Baker et al., 2021). The study also aimed to explore the impact of the training on resilience, wellbeing and burnout.

Design/methodology/approach
In a within-subject 10-week follow-up study, mixed methods were used to evaluate the one-day resilience training for trainee mental health professionals working in services in the UK.

Findings
The intervention was found to be acceptable to attendees, with high levels of satisfaction reported. Resilience was evaluated through self-report measures at three-time points. Resilience scores at follow-up were significantly higher than pre- and post-intervention scores. The secondary outcomes of wellbeing and burnout did not significantly improve.

Research limitations/implications
Preliminary support was found for the feasibility and acceptability of resilience training for trainee mental health practitioners. Audience-specific adaptations and follow-up groups to aid skills practice and implementation may further enhance benefits to resilience. Resilience interventions may supplement practitioner training to improve resilience. Resilience is associated with higher wellbeing and lower burnout. The impact of resilience training on overall wellbeing and burnout remains uncertain; however, newly learned resilience skills may take time to benefit wellbeing.

Originality/value
A key contribution of this study is to provide evidence regarding the feasibility of implementing the skills-based model of personal resilience, outlined in Baker et al. (2021), in a learning environment.
“The roughest form of social work:” How court officials justify bail decisions
Authors: Winter Alix S. , Clair Matthew 
Published: September 2023

AbstractGrowing research has analyzed quantitative patterns of bail decisions and outcomes, but we know far less about how court officials justify their bail decisions. To enhance understanding of how bail decisions—and their resulting pretrial outcomes—are generated, we interviewed 104 judges, prosecutors, and public defenders in a northeastern state. Court officials in our study reported three primary justifications at bail: ensuring defendants return to court, preventing crime, and lessening harm. The first two justifications have been suggested in the literature, but the latter is novel and encompasses two secondary justifications: lessening criminal legal system harm and lessening societal harm. We show how these justifications and the decisions they enable blend risk management with rehabilitation and emerge from court officials’ shared assumption of defendants’ social marginality but varied beliefs about what to do about such marginality pretrial. Each justification allows for distinct, but at times overlapping, bail decisions. We discuss the implications of our findings for theories of court official decision‐making, research on racial and socioeconomic inequality, and bail reform policy.