bluuebunny/crossref_metadata_2025_split huggingface dataset:
STARQ: Domain-Invariant Brainstem Nuclei Segmentation and Signal Quantification
Authors: Kaiser Julia , Luong Dana , Sung Eunseo , Iqbal Asim , Sahni Vibhu 
Published: November 2023

AbstractBrainstem nuclei are hard to distinguish due to very few distinctive features which makes detecting them with high accuracy extremely difficult. We introduce StARQ that builds on SeBRe, a deep learning-based framework to segment regions of interest. StARQ provides new functionalities for automated segmentation of brainstem nuclei at high granularity, and quantification of underlying neural features such as axonal tracings, and synaptic punctae. StARQ will serve as a toolbox for generalized brainstem analysis, enabling reliable high-throughput computational analysis with open-source models.
Bidirectional chemogenetic modulation of claustral activity causes altered cortical dynamics
Authors: Zahacy Ryan , Ma Yonglie , Winship Ian R. , Jackson Jesse , Chan Allen W. 
Published: November 2023

AbstractIn recent years, there has been a growing interest in understanding the function of the claustrum. The claustrum is a thin, long, subcortical structure with dense connections to the cortex. Despite these extensive connections, the manner in which the claustrum influences broader cortical activity remains unclear. We used mesoscale calcium fluorescence imaging to examine resting state cortical activity (1-5Hz) and sensory-evoked responses in lightly anesthetized mice, before and after bi-directional chemogenetic modulation of claustrum-prefrontal neurons. Claustrum inhibition resulted in increased activity in anterior-medial cortical areas, whereas claustrum excitation resulted in decreased activity in anterior-medial cortical regions. Claustrum inhibition also led to an increased local coupling between areas of frontal cortex, a decreased correlation between anterior medial regions-of-interest (ROIs) and lateral and posterior ROIs, and an increased sensory evoked response in the visual cortex. These results are consistent with the finding that the claustrum has a large feed-forward inhibitory effect on the PFC, and the concept that specific claustrocortical pathways may modulate recruit and synchronize activity in topographically distinct cortical modules. Together these results show that neural activity in the claustrum modulates the excitability of prefrontal cortical networks, suggesting a potential target for prefrontal-dependent behaviors such as learning, attention, and stress regulation.
CONSULT-II: Accurate taxonomic identification and profiling using locality-sensitive hashing
Authors: Şapcı Ali Osman Berk , Rachtman Eleonora , Mirarab Siavash 
Published: November 2023

AbstractTaxonomic classification of short reads and taxonomic profiling of metagenomic samples are well-studied yet challenging problems. The presence of species belonging to ranks without close representation in a reference dataset is particularly challenging. While k-mer-based methods have performed well in terms of running time and accuracy, they tend to have reduced accuracy for such novel species. Here, we show that using locality-sensitive hashing (LSH) can increase the sensitivity of the k-mer-based search. Our method, which combines LSH with several heuristics techniques including soft LCA labeling and voting is, more accurate than alternatives in both taxonomic classification of individual reads and abundance profiling.
Prevalence of Avian Influenza Virus in Synanthropic Birds Associated with an Outbreak of Highly Pathogenic Strain EA/AM H5N1
Authors: Ringenberg Jourdan M. , Weir Kelsey , Humberg Lee , Voglewede Carl , Oswald Mitch , Root J. Jeffrey , Dilione Krista , Casey Evan , Milleson Michael , Linder Timothy , Lenoch Julianna 
Published: November 2023

AbstractThe 2022 – 2023 highly pathogenic avian influenza (HPAI) virus outbreak of H5N1 Eurasian lineage goose/Guangdong clade 2.3.4.4b is the largest in North American history and has significantly impacted wild bird populations and domestic poultry across the United States. Synanthropic birds may play an important role in transmitting the virus laterally to other wild bird species and domestic poultry. Understanding the prevalence of HPAI H5N1 in different avian orders may help inform management decisions and potential risk factors for both wild and domestic bird populations. Following the confirmation of infection of HPAI H5N1 in domestic poultry at two commercial premises in IN, USA, we sampled and tested 266 synanthropic avian species within the Columbiformes and Passeriformes orders and found no detection of the virus at either location. Additionally, laboratories within the National Animal Health Laboratory Network were queried for influenza Type A rRT-PCR assay test results from morbidity and mortality events in wild birds, consisting of 10,786 birds tested across eight orders and 1,666 avian influenza virus detections. Query results were assessed by taxonomic groups for viral prevalence and suggested that the virus most often was observed in predatory and scavenging birds. Although detections were found in non-predatory synanthropic birds including the orders Columbiformes, Galliformes, and Passeriformes, the risk of transmission from and between these groups appears comparatively low, with apparent prevalence rates of 0.0090, 0.0688, and 0.0147, respectively. The highest prevalence was observed in raptors (0.2514), with prevalence rates in exclusively scavengingCathartidaereaching up to 0.5333. There is strong evidence that consumption of infected tissues is a key pathway for transmission of avian influenza viruses. Understanding the impact of the 2022 – 2023 HPAI outbreak in wild bird populations can provide pertinent information on viral transmission, disease ecology, and risk to humans and agriculture.
A Novel human IL-23A Overexpressing Mouse Model of Systemic Lupus Erythematosus
Authors: Christodoulou-Vafeiadou Eleni , Geka Christina , Iliopoulou Lida , Ntari Lydia , Denis Maria C. , Karagianni Niki , Kollias George 
Published: November 2023

AbstractObjectiveInterleukin-23 (IL-23) is a crucial cytokine implicated in chronic inflammation and autoimmunity, associated with various diseases like psoriasis, psoriatic arthritis, and systemic lupus erythematosus (SLE). This study aimed to create and characterize a transgenic mouse model (TghIL23A) overexpressing human IL23A, providing a valuable tool for investigating the pathogenic role of hIL23A and evaluating the efficacy of anti-human-IL23A therapeutics.MethodsTghIL23A mice were generated via microinjection of CBAxC57BL/6 zygotes with a fragment of the human IL23A gene, flanked by its 5’-regulatory sequences and the 3’UTR of human beta-globin. The TghIL23A pathology was assessed through hematological and biochemical analyses, cytokine and anti-nuclear antibody detection, histopathological examination of skin and renal tissues. The response to the anti-hIL23A therapeutic agent guselkumab, was evaluated in groups of 8 mixed-sex mice receiving subcutaneous treatment twice weekly for 10 weeks, using clinical, biomarker and histopathological readouts.ResultsTghIL23A mice exhibited interactions between hIL23A and mouse IL23/IL12p40, and developed a chronic multiorgan autoimmune disease marked by proteinuria, anti-dsDNA antibodies, severe inflammatory lesions in the skin and milder phenotypes in the kidneys and lungs. The TghIL23A pathological features exhibited significant similarities to those observed in human SLE patients.ConclusionsWe have generated and characterized a novel genetic mouse model of SLE, providing proof-of-concept for the etiopathogenic role of hIL-23A. This new model has a normal lifespan and integrates several characteristics of the human disease’s complexity and chronicity making it an attractive preclinical tool for studying IL23-dependent pathogenic mechanisms and assessing the efficacy of anti-hIL23A or modeled disease-related therapeutics.
Temperature influences the excretion time and parasitic load ofTrypanosoma cruziin theTriatoma infestansvector
Authors: Álvarez-Duhart B. , Clavijo-Baquet S. , Valenzuela-Perez L. , Maya J.D. , Saavedra M. , Ortiz S. , Muñoz-San Martín C. , Bacigalupo A. , Cattan P. E. 
Published: November 2023

AbstractTrypanosoma cruziis a protozoan parasite transmitted by triatomine insect vectors, which expel their infectious dejections when they feed, causing Chagas disease in humans. The transmission and incidence of this vector-borne disease depend on the vital traits of its vectors, includingTriatoma infestans, the main vector in Southern South America. Being an ectothermic species, its metabolism and its vital traits respond to temperature fluctuations. Here, we evaluated if changes in the average and variability of temperature expected with climate change modify: (i) the extrinsic incubation period (EIP) ofT. cruziwithin the vectorT. infestans, (ii) its parasitic load, and (iii) the probability that its dejections wereT. cruzi-positive. We acclimated triatomines infected with Dm28cT. cruzistrain to two constant and two variable temperature treatments and measuredT. cruziin their dejections by qPCR over a 42-day period. We observed that individuals in warm-temperature treatments showed lower EIP and higher parasitic load than cold-temperature treatments. Also, temperature variability can increase the parasitic load peak in cold-temperature treatments. Consequently, in a climate change scenario, there might be an increase in the vector capacity ofT. infestansand probably a change in the risk of vectorial transmission ofT. cruzi.
Fibrillar adhesion dynamics govern the timescales of nuclear mechano-response via the vimentin cytoskeleton
Authors: Beedle Amy E.M. , Jaganathan Anuja , Albajar-Sigalés Aina , Yavitt F. Max , Bera Kaustav , Andreu Ion , Granero-Moya Ignasi , Zalvidea Dobryna , Kechagia Zanetta , Wiche Gerhard , Trepat Xavier , Ivaska Johanna , Anseth Kristi S. , Shenoy Vivek B. , Roca-Cusachs Pere 
Published: November 2023

AbstractThe cell nucleus is continuously exposed to external signals, of both chemical and mechanical nature. To ensure proper cellular response, cells need to regulate not only the transmission of these signals, but also their timing and duration. Such timescale regulation is well described for fluctuating chemical signals, but if and how it applies to mechanical signals reaching the nucleus is still unknown. Here we demonstrate that the formation of fibrillar adhesions locks the nucleus in a mechanically deformed conformation, setting the mechanical response timescale to that of fibrillar adhesion remodelling (∼1 hour). This process encompasses both mechanical deformation and associated mechanotransduction (such as via YAP), in response to both increased and decreased mechanical stimulation. The underlying mechanism is the anchoring of the vimentin cytoskeleton to fibrillar adhesions and the extracellular matrix through plectin 1f, which maintains nuclear deformation. Our results reveal a mechanism to regulate the timescale of mechanical adaptation, effectively setting a low pass filter to mechanotransduction.
Opening the species box: What parsimonious microscopic models of speciation have to say about macroevolution
Authors: Couvert Élisa , Bienvenu François , Duchamps Jean-Jil , Erard Adélie , Miró Pina Verónica , Schertzer Emmanuel , Lambert Amaury 
Published: November 2023

AbstractIn the last two decades, lineage-based models of diversification, where species are viewed as particles that can divide (speciate) or die (become extinct) at rates depending on some evolving trait, have been very popular tools to study macroevolutionary processes. Here, we argue that this approach cannot be used to break down the inner workings of species diversification and that “opening the species box” is necessary to understand the causes of macroevolution, but that too detailed speciation models also fail to make robust macroevolutionary predictions.We set up a general framework for parsimonious models of speciation that rely on a minimal number of mechanistic principles: (i) reproductive isolation is caused by excessive dissimilarity between genotypes; (ii) dissimilarity results from a balance between differentiation processes and homogenizing processes; and (iii) dissimilarity can feed back on these processes by decelerating homogenization.We classify such models according to the main homogenizing process : (1) clonal evolution models (ecological drift), (2) models of genetic isolation (gene flow) and (3) models of isolation by distance (spatial drift). We review these models and their specific predictions on macroscopic variables such as species abundances, speciation rates, interfertility relationships or phylogenetic tree structure.We propose new avenues of research by displaying conceptual questions remaining to be solved and new models to address them: the failure of speciation at secondary contact, the feedback of dissimilarity on homogenization, the emergence in space of breeding barriers.
SOX4 exerts contrasting regulatory effects on labor-associated gene promoters in myometrial cells
Authors: Khader Nawrah , Shchuka Virlana M. , Dorogin Anna , Shynlova Oksana , Mitchell Jennifer A. 
Published: November 2023

AbstractThe uterine muscular layer, or myometrium, undergoes profound changes in global gene expression during its progression from a quiescent state during pregnancy to a contractile state at the onset of labor. In this study, we investigate the role of SOX family transcription factors in myometrial cells and provide evidence for the role of SOX4 in regulating labor-associated genes. We show thatSox4has elevated expression in the murine myometrium during a term laboring process and in two mouse models of preterm labor. Additionally, SOX4 differentially affects labor-associated gene promoter activity in cooperation with activator protein 1 (AP-1) dimers. SOX4 exerted no effect on theGja1promoter; a JUND-specific activation effect at theFospromoter; a positive activation effect on theMmp11promoter with the AP-1 dimers; and surprisingly, we noted that the reporter expression of thePtgs2promoter in the presence of JUND and FOSL2 was repressed by the addition of SOX4. Our data indicate SOX4 may play a diverse role in regulating gene expression in the laboring myometrium in cooperation with AP-1 factors. This study enhances our current understanding of the regulatory network that governs the transcriptional changes associated with the onset of labor and highlights a new molecular player that may contribute to the labor transcriptional program.
Comparison of radiography and computed tomography for condylar fracture risk assessment in Thoroughbred racehorses
Authors: Irandoust S. , O’Neil L. , Stevenson C.M. , Franseen F.M. , Ramzan P.H.L. , Powell S.E. , Brounts S.H. , Loeber S.J. , Ergun D.L. , Whitton R.C. , Henak C.R. , Muir P. 
Published: November 2023

AbstractBackgroundCatastrophic injury has a low incidence but leads to the death of many Thoroughbred racehorses annually. Effective screening for injury risk needs to solve the false negative diagnostic sensitivity problem.ObjectivesTo determine sensitivity, specificity, and reliability for condylar stress fracture risk assessment from fetlock digital radiographs (DR) and standing computed tomography (sCT) imaging (Asto CT Equina®).Study designControlledex vivoexperiment.MethodsA blinded set of DR and sCT images of the thoracic limb fetlock were prepared from 31 Thoroughbred racehorses and reviewed by four veterinarians. Observers evaluated the condyles and parasagittal grooves (PSG) of the third metacarpal subchondral bone (MC3) for the extent of dense bone and lucency/fissure and assigned a risk assessment grade for condylar stress fracture based on imaging findings. Sensitivity and specificity for detection of subchondral structural changes in the condyles and PSG of the third metacarpal bone and for risk assessment for condylar stress fracture were determined by comparison with a reference assessment. Agreement between each observer and the reference assessment and reliability between observers were determined. Intra-observer repeatability was also assessed.ResultsIntra-observer repeatability was identified for both DR and sCT imaging. Sensitivity for detection of structural change was lower than specificity for both imaging methods and all observers. For horses with a normal level of risk, observer assessment often agreed with the reference assessment. Sensitivity for risk assessment was lower than specificity for all observers. For horses with a high risk of serious injury, observers generally underestimated the level of risk. Diagnostic sensitivity of risk assessment was improved with sCT imaging, particularly for horses with elevated risk of injury. Assessment reliability was better with sCT than DR.Main limitationsTheex vivostudy design influenced DR image sets regarding limb positioning and image contrast compared within vivoDR imaging.ConclusionsRisk assessment through screening with diagnostic imaging is a promising approach to improve injury prevention in racing Thoroughbreds. Knowledge of sensitivity and specificity of fetlock lesion detection by DR and sCT provides critical guidance regarding development of improved screening programs for racehorses using diagnostic imaging. We found improved detection of MC3 subchondral structural change and risk assessment for condylar stress fracture with sCTex vivo.
Democratizing Protein Language Models with Parameter-Efficient Fine-Tuning
Authors: Sledzieski Samuel , Kshirsagar Meghana , Baek Minkyung , Berger Bonnie , Dodhia Rahul , Ferres Juan Lavista 
Published: November 2023

AbstractProteomics has been revolutionized by large pre-trained protein language models, which learn unsupervised representations from large corpora of sequences. The parameters of these models are then fine-tuned in a supervised setting to tailor the model to a specific downstream task. However, as model size increases, the computational and memory footprint of fine-tuning becomes a barrier for many research groups. In the field of natural language processing, which has seen a similar explosion in the size of models, these challenges have been addressed by methods for parameter-efficient fine-tuning (PEFT). In this work, we newly bring parameter-efficient fine-tuning methods to proteomics. Using the parameter-efficient method LoRA, we train new models for two important proteomic tasks: predicting protein-protein interactions (PPI) and predicting the symmetry of homooligomers. We show that for homooligomer symmetry prediction, these approaches achieve performance competitive with traditional fine-tuning while requiring reduced memory and using three orders of magnitude fewer parameters. On the PPI prediction task, we surprisingly find that PEFT models actually outperform traditional fine-tuning while using two orders of magnitude fewer parameters. Here, we go even further to show that freezing the parameters of the language model and training only a classification head also outperforms fine-tuning, using five orders of magnitude fewer parameters, and that both of these models outperform state-of-the-art PPI prediction methods with substantially reduced compute. We also demonstrate that PEFT is robust to variations in training hyper-parameters, and elucidate where best practices for PEFT in proteomics differ from in natural language processing. Thus, we provide a blueprint to democratize the power of protein language model tuning to groups which have limited computational resources.
Navigating the manifold of single-cell gene coexpression to discover interpretable gene programs
Authors: Ozbay Sinan , Parekh Aditya , Singh Rohit 
Published: November 2023

AbstractDuring development and differentiation, transcriptional regulation in the cell often occurs at the level of gene programs (i.e., sets of co-varying genes), rather than isolated genes. It is therefore crucial to identify differential program expression over time, or across case-vs-control samples. However, this has remained difficult: gene programs are inferred by analyzing gene coexpression, and mathematical operations on the latter are nontrivial. Gene coexpression is quantified as a symmetric positive-definite matrix, on which even basic quantities such as arithmetic differences are neither mathematically sound nor biologically interpretable. Here we exploit the structure of the Riemannian manifold of gene coexpression matrices to propose a novel abstraction of gene coexpression that is mathematically well-founded while being computationally tractable and statistically rigorous. Importantly, it also captures biological similarity better than standard coexpression. This conceptual advance enables us to introduce Sceodesic, an algorithm that invokes the log-Euclidean metric from differential geometry to quantify coexpression patterns specific to each cell state, and organizes them into a study-wide panel of interpretable gene programs. Applied to nine single-cell RNA-seq datasets, Sceodesic outperforms existing methods in early detection of cell fate commitment by leveraging differential expression of gene programs, and is also effective in discovering disease-linked programs in multi-sample studies. By respecting the manifold of gene coexpression matrices, Sceodesic resolves a longstanding challenge in relating biological variability to statistical analyses of single-cell RNA-seq data and enables the discovery of gene programs driving differentiation and disease.Software availabilityhttps://singhlab.net/Sceodesic
Minimization of the E. coli ribosome, aided and optimized by community science
Authors: Tangpradabkul Tiyaporn , Palo Michael , Townley Jill , Hsu Kenneth B. ,   Eterna participants, Smaga Sarah , Das Rhiju , Schepartz Alanna 
Published: November 2023

ABSTRACTThe ribosome is a ribonucleoprotein complex found in all domains of life. Its role is to catalyze protein synthesis, the messenger RNA (mRNA)-templated formation of amide bonds between α-amino acid monomers. Amide bond formation occurs within a highly conserved region of the large ribosomal subunit known as the peptidyl transferase center (PTC). Here we describe the stepwise design and characterization of mini-PTC 1.1, a 284-nucleotide RNA that recapitulates many essential features of theEscherichia coliPTC. Mini-PTC 1.1 folds into a PTC-like structure under physiological conditions, even in the absence of r-proteins, and engages small molecule analogs of A- and P-site tRNAs. The sequence of mini-PTC 1.1 differs from the wild typeE. coliribosome at 12 nucleotides that were installed by a cohort of citizen scientists using the on-line video game Eterna. These base changes improve both the secondary structure and tertiary folding of mini-PTC 1.1 as well as its ability to bind small molecule substrate analogs. Here, the combined input from Eterna citizen-scientists and RNA structural analysis provides a robust workflow for the design of a minimal PTC that recapitulates many features of an intact ribosome.