bluuebunny/crossref_metadata_2025_split huggingface dataset:
Choice of friction coefficient deeply affects tissue behaviour in stochastic epithelial vertex models
Authors: Guerrero Pilar , Perez-Carrasco Ruben 
Published: March 2024

To understand the mechanisms that coordinate the formation of biological tissues, the use of numerical implementations is necessary. The complexity of such models involves many assumptions and parameter choices that result in unpredictable consequences, obstructing the comparison with experimental data. Here, we focus on vertex models, a family of spatial models used extensively to simulate the dynamics of epithelial tissues. Usually, in the literature, the choice of the friction coefficient is not addressed using quasi-static deformation arguments that generally do not apply to realistic scenarios. In this manuscript, we discuss the role that the choice of friction coefficient has on the relaxation times and consequently in the conditions of cell cycle progression and division. We explore the effects that these changes have on the morphology, growth rate and topological transitions of the tissue dynamics. These results provide a deeper understanding of the role that an accurate mechanical description plays in the use of vertex models as inference tools.
This article is part of a discussion meeting issue ‘Causes and consequences of stochastic processes in development and disease’.
Krüppel-like Factor (KLF) family members control expression of genes required for serous cavity and alveolar macrophage identities
Authors: Pestal Kathleen , Slayden Leianna C , Barton Gregory M 
Published: March 2024

ABSTRACTTissue-resident macrophages adopt distinct gene expression profiles and exhibit functional specialization based on their tissue of residence. Recent studies have begun to define the signals and transcription factors that induce these identities. Here we describe an unexpected and specific role for the broadly expressed transcription factor Kruppel-like Factor 2 (KLF2) in the development of embryonically derived Large Cavity Macrophages (LCM) in the serous cavities. KLF2 not only directly regulates the transcription of genes previously shown to specify LCM identity, such as retinoic acid receptors and GATA6, but also is required for induction of many other transcripts that define the identity of these cells. We identify a similar role for KLF4 in regulating the identity of alveolar macrophages in the lung. These data demonstrate that broadly expressed transcription factors, such as Group 2 KLFs, can play important roles in the specification of distinct identities of tissue-resident macrophages.SUMMARYPrevious studies have identified many specific regulators of macrophage development. This work reveals the requirement of members of the Group 2 KLF transcription factor family in the determination of the identity of distinct tissue-resident macrophages.
Conformational Ensembles Reveal the Origins of Serine Protease Catalysis
Authors: Du Siyuan , Kretsch Rachael C. , Parres-Gold Jacob , Pieri Elisa , Cruzeiro Vinícius Wilian D. , Zhu Mingning , Pinney Margaux M. , Yabukarski Filip , Schwans Jason P. , Martínez Todd J. , Herschlag Daniel 
Published: March 2024

AbstractEnzymes exist in ensembles of states that encode the energetics underlying their catalysis. Conformational ensembles built from 1231 structures of 17 serine proteases reveal atomic-level changes across their reaction states, identify molecular features that provide catalysis, and quantify their energetic contributions to catalysis. These enzymes precisely position their reactants in destabilized conformers, creating a downhill energetic gradient that selectively favors the motions required for reaction while limiting off-pathway conformational states. A local catalytic motif, the “nucleophilic elbow”, has repeatedly evolved, generating ground state destabilization in 50 proteases and 52 additional enzymes spanning 32 distinct structural folds. Ensemble–function analyses reveal previously unknown catalytic features, provide quantitative models based on simple physical and chemical principles, and identify motifs recurrent in Nature that may inspire enzyme design.One sentence summary:Ensemble–function analyses provide a quantitative model for serine protease catalysis, reveal previously unknown conformational features that contribute to their catalysis, and identify a structural motif that underlie these features and has evolved in >100 different enzymes from 32 protein folds.
Human calpain-3 and its structural plasticity: dissociation of a homohexamer into dimers on binding titin
Authors: Ye Qilu , Henrickson Amy , Demeler Borries , Serrão Vitor Hugo Balasco , Davies Peter L. 
Published: March 2024

AbstractCalpain-3 is an intracellular Ca2+-dependent cysteine protease abundant in skeletal muscle. Its physiological role in the sarcomere is thought to include removing damaged muscle proteins after exercise. Loss-of-function mutations in its single-copy gene cause a dystrophy of the limb-girdle muscles. These mutations, of which there are over 500 in humans, are spread all along this 94-kDa multi-domain protein that includes three 40+-residue sequences (NS, IS1, and IS2). The latter sequences are unique to this calpain isoform and are hypersensitive to proteolysis. To investigate the whole enzyme structure and how mutations might affect its activity, we produce the proteolytically more stable 85-kDa calpain-3 ΔNS ΔIS1 form with a C129A inactivating mutation as a recombinant protein inE. coli. During size-exclusion chromatography, this calpain-3 was consistently eluted as a much larger 0.5-MDa complex rather than the expected 170-kDa dimer. Its size, which was confirmed by SEC-MALS, Blue Native PAGE, and AUC, made the complex amenable to single-particle cryo-EM analysis. From two data sets, we obtained a 3.85-Å reconstruction map that shows the complex is a trimer of calpain-3 dimers with six penta-EF-hand domains at its core. Calpain-3 has been reported to bind the N2A region of the giant muscle protein titin. When this 37-kDa region of titin was co-expressed with calpain-3 the multimer was reduced to a 320-kDa particle, which appears to be the calpain dimer bound to several copies of the titin fragment. We suggest that newly synthesized calpain-3 is kept as an inactive hexamer until it binds the N2A region of titin in the sarcomere, whereupon it dissociates into functional dimers.
Auditory Feature-based Perceptual Distance
Authors: Chen Shukai , Thielk Marvin , Gentner Timothy Q. 
Published: March 2024

AbstractStudies comparing acoustic signals often rely on pixel-wise differences between spectrograms, as in for example mean squared error (MSE). Pixel-wise errors are not representative of perceptual sensitivity, however, and such measures can be highly sensitive to small local signal changes that may be imperceptible. In computer vision, high-level visual features extracted with convolutional neural networks (CNN) can be used to calculate the fidelity of computer-generated images. Here, we propose the auditory perceptual distance (APD) metric based on acoustic features extracted with an unsupervised CNN and validated by perceptual behavior. Using complex vocal signals from songbirds, we trained a Siamese CNN on a self-supervised task using spectrograms rescaled to match the auditory frequency sensitivity of European starlings, Sturnus vulgaris. We define APD for any pair of sounds as the cosine distance between corresponding feature vectors extracted by the trained CNN. We show that APD is more robust to temporal and spectral translation than MSE, and captures the sigmoidal shape of typical behavioral psychometric functions over complex acoustic spaces. When fine-tuned using starlings’ behavioral judgments of naturalistic song syllables, the APD model yields even more accurate predictions of perceptual sensitivity, discrimination, and categorization on novel complex (high-dimensional) acoustic dimensions, including diverging decisions for identical stimuli following different training conditions. Thus, the APD model outperforms MSE in robustness and perceptual accuracy, and offers tunability to match experience-dependent perceptual biases.
Inkject Printed Graphene Microelectrodes for Real-Time Impedance Spectroscopy of Neural Cells in Organ-on-a-Chip
Authors: Gabriel Ouedraogo Lionel Jean , Hashemi Nicole N. 
Published: March 2024

AbstractThis study presents the development and characterization of a graphene-based sensor integrated into a microfluidic chip for real-time monitoring of cell growth and viability. The sensor fabrication involved the metabolization of graphene from graphite using a simple and cost-effective method. The sensor design, created using Solidworks, featured electrodes capable of detecting environmental changes through impedance sensing. A mold was created using a cutter plotter to overcome challenges in achieving the desired sensor shape, and the electrodes were printed on a polyester (PETE) membrane. The conductivity of the electrodes was optimized through annealing, considering the temperature limits of the membrane. Annealing at 150 °C for 40 minutes yielded electrodes with desired conductivity and maintained membrane integrity. Compatibility with cellular growth was confirmed through cell culture experiments. The scaled electrodes were integrated into a microfluidic chip, and their performance was evaluated using cyclic voltammetry and electrochemical impedance spectroscopy. The results demonstrated the successful functioning of the electrodes within the chip. The developed graphene-based sensor offers promising applications in cellular studies and biosensing through real-time monitoring of cell growth and viability was achieved by measuring impedance changes resulting from cell attachment.
Association analysis between an epigenetic alcohol risk score and blood pressure
Authors: Bui Helena , Keshawarz Amena , Wang Mengyao , Lee Mikyeong , Ratliff Scott M. , Lin Lisha , Birditt Kira S. , Faul Jessica D. , Peters Annette , Gieger Christian , Delerue Thomas , Kardia Sharon L. R. , Zhao Wei , Guo Xiuqing , Yao Jie , Rotter Jerome I. , Li Yi , Liu Xue , Liu Dan , Tavares Juliana F. , Pehlivan Gökhan , Breteler Monique M.B. , Karabegovic Irma , Ochoa-Rosales Carolina , Voortman Trudy , Ghanbari Mohsen , van Meurs Joyce B.J. , Nasr Mohamed Kamal , Dörr Marcus , Grabe Hans J. , London Stephanie J. , Teumer Alexander , Waldenberger Melanie , Weir David R. , Smith Jennifer A. , Levy Daniel , Ma Jiantao , Liu Chunyu 
Published: March 2024

AbstractBackgroundEpigenome-wide association studies have revealed multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases.ResultsWe generated an alcohol consumption epigenetic risk score (ERS) based on previously reported 144 alcohol-associated CpGs and examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. We found an association of alcohol intake with the ERS in the meta-analysis with 0.09 units higher ERS per drink consumed per day (p< 0.0001). Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p= 4.64E-07), 0.68 mm Hg higher DBP (p= 0.006), and an odds ratio of 1.78 for HTN (p< 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with blood pressure levels, i.e., a one-unit increase in ERS was associated with 0.74 (p= 0.002) and 0.50 (p= 0.0006) mm Hg higher SBP and DBP, but could not confirm the association with hypertension. Longitudinal analyses in FHS (n = 3,260) and five independent external cohorts (n = 4,021) showed that the baseline ERS was not associated with a change in blood pressure over time or with incident HTN.ConclusionsOur findings provide proof-of-concept that utilizing an ERS is a useful approach to capture the recent health consequences of lifestyle behaviors such as alcohol consumption.
Compound-SNE: Comparative alignment of t-SNEs for multiple single-cell omics data visualisation
Authors: Cess Colin G. , Haghverdi Laleh 
Published: March 2024

AbstractOne of the first steps in single-cell omics data analysis is visualization, which allows researchers to see how well-separated cell-types are from each other. When visualizing multiple datasets at once, data integration/batch correction methods are used to merge the datasets. While needed for downstream analyses, these methods modify features space (e.g. gene expression)/PCA space in order to mix cell-types between batches as well as possible. This obscures sample-specific features and breaks down local embedding structures that can be seen when a sample is embedded alone. Therefore, in order to improve in visual comparisons between large numbers of samples, we introduce Compound-SNE, which performs what we term a soft alignment of samples in embedding space. We show that Compound-SNE is able to align cell-types in embedding space across samples and data modalities, while preserving local embedding structures from when samples are embedded independently.
Brassinosteroid and gibberellin signaling are required for Tomato internode elongation in response to low red: far-red light
Authors: Li Linge , Wonder Jesse , Helming Ticho , van Asselt Gijs , Pantazopoulou Chrysoula K. , van de Kaa Yorrit , Kohlen Wouter , Pierik Ronald , Kajala Kaisa 
Published: March 2024

AbstractIn this study, we explore the dynamic interplay between the plant hormones gibberellins (GA), brassinosteroids (BR), and Indole-3-Acetic Acid (IAA) in their collective impact on plant shade avoidance elongation under varying light conditions. We focus particularly on low Red: Far-red (R:FR) light conditions achieved by supplementing the background light with FR. Our research delves into how these hormones individually and synergistically influence stem elongation in tomato plants. Through meticulous experimental modulations of GA, IAA, and BR, we demonstrate that GA and BR are sufficient but also necessary for inducing stem elongation under low R:FR light conditions. Intriguingly, while IAA alone shows limited effects, its combination with GA yields significant elongation, suggesting a nuanced hormonal balance. Furthermore, we unveil the complex interplay of these hormones under light with low R:FR, where the suppression of one hormone’s effect can be compensated by the others. This study provides insights into the hormonal mechanisms governing plant adaptation to light, highlighting the intricate and adaptable nature of plant growth responses. Our findings have far-reaching implications for agricultural practices, offering potential strategies for optimizing plant growth and productivity in various lighting environments.HighlightThis study unveils the interplay of brassinosteroids and gibberellins in shade avoidance elongation, revealing how tomatoes acclimate in response to far-red enriched light conditions.
Social transmission of inflammation in mice
Authors: Quintana Silvia Castany , Da Rosa Priscila Batista , Shionoya Kiseko , Blomqvist Anders , Engblom David 
Published: March 2024

AbstractThe ability to detect and respond to sickness in others promotes survival. Here we show that mouse dams respond to immune challenged pups by mirroring their inflammatory response. Thus, dams with pups subjected to immune challenge displayed a marked induction of inflammatory mediators in both the brain and the periphery, accompanied by an increase in maternal behaviors and corticosterone levels. This social transmission of inflammation did not require physical contact, and it contributed to the stress hormone response in the dams. In adult dyads, interaction with an immune challenged cagemate did not elicit robust inflammatory signaling but induced an increased responsiveness to a subsequent immune challenge. The identification of social transmission of inflammation, or inflammatory responsiveness, may open new avenues for research on social behavior, just like the description of similar phenomena such as observational fear and transmitted pain have done.
Unveiling the Power of High-Dimensional Cytometry Data with cyCONDOR
Authors: Kroeger Charlotte , Müller Sophie , Leidner Jacqueline , Kröber Theresa , Warnat-Herresthal Stefanie , Spintge Jannis Bastian , Zajac Timo , Frolov Aleksej , Carraro Caterina , Puccio Simone , Schultze Joachim L , Pecht Tal , Beyer Marc D , Bonaguro Lorenzo 
Published: March 2024

AbstractHigh-dimensional cytometry (HDC) is a powerful technology for studying single-cell phenotypes in complex biological systems. Although technological developments and affordability have made HDC broadly available in recent years, technological advances were not coupled with an adequate development of analytical methods that can take full advantage of the complex data generated. While several analytical platforms and bioinformatics tools have become available for the analysis of HDC data, these are either web-hosted with limited scalability or designed for expert computational biologists, making their use unapproachable for wet lab scientists. Additionally, end-to-end HDC data analysis is further hampered due to missing unified analytical ecosystems, requiring researchers to navigate multiple platforms and software packages to complete the analysis.To bridge this data analysis gap in HDC we developedcyCONDOR, aneasy-to-usecomputational framework covering not only all essential steps of cytometry data analysis but also including an array of downstream functions and tools to expand the biological interpretation of the data. The comprehensive suite of features ofcyCONDOR, including guided pre-processing, clustering, dimensionality reduction, and machine learning algorithms, facilitates the seamless integration ofcyCONDORinto clinically relevant settings, where scalability and disease classification are paramount for the widespread adoption of HDC in clinical practice. Additionally, the advanced analytical features ofcyCONDOR, such as pseudotime analysis and batch integration, provide researchers with the tools to extract deeper insights from their data. We usedcyCONDORon a variety of data from different tissues and technologies demonstrating its versatility to assist the analysis of high dimensionality data from preprocessing to biological interpretation.
Uncovering the genetic diversity inAedes aegyptiinsecticide resistance genes through global comparative genomics
Authors: Spadar Anton , Collins Emma , Messenger Louisa A. , Clark Taane G. , Campino Susana 
Published: March 2024

ABSTRACTInsecticides are essential to control the transmission of vector-borne diseases to humans and animals, but their efficacy is being threatened by the spread of resistance across multiple medically important mosquito species. An example of this isAedes aegypti- a major vector of arboviruses, including Zika, dengue, yellow fever, West Nile, and Chikungunya, with widespread insecticide resistance reported in the Americas and Asia, while data from Africa is more limited. Here we investigate the global genetic diversity in four insecticide resistance associated genes:ace-1,GSTe2,rdlandvgsc.Apart fromvgsc, the other genes have been less investigated inAe. aegypti, and limited genetic diversity information is available. We explore a large whole-genome sequencing dataset of 729Ae. aegyptiacross 15 countries including nine in Africa. Among the four genes, we identified 1,829 genetic variants including 474 non-synonymous substitutions, as well as putative copy number variations inGSTe2andvgsc. Among these are many previously documented insecticide resistance mutations which were present at different frequencies and combinations depending on origin of samples. Global insecticide resistance phenotypic data demonstrated variable resistance in geographic areas with resistant genotypes. These warrant further investigation to assess their functional contribution to insecticide resistant phenotypes and their potential development into genetic panels for operational surveillance. Overall, our work provides the first global catalogue and geographic distribution of known and new amino-acid mutations and duplications that can be used to guide the identification of resistance drivers inAe. aegyptiand thereby support monitoring efforts and strategies for vector control.
M. bovisPPD Enhances Respiratory Bioenergetics of Human vs. Bovine Macrophages
Authors: Bartens Marie-Christine , Willcocks Sam , Werling Dirk , Gibson Amanda J. 
Published: March 2024

AbstractThe role of macrophage (MØ) cellular metabolism and reprogramming during TB infection is of great interest due to the influence ofMycobacteriumspp. on MØ bioenergetics. Recent studies have shown thatM. tuberculosisinduces a TLR2-dependent shift towards aerobic glycolysis and metabolic reprogramming, comparable to the established LPS induced pro-inflammatory M1 MØ polarisation. Distinct differences in the metabolic profile of murine and human MØ indicates species-specific differences in bioenergetics. So far, studies examining the metabolic potential of cattle are lacking, thus the basic bioenergetics of bovine and human MØ were explored in response to a variety of innate immune stimuli. Cellular energy metabolism kinetics were measured concurrently for both species on a Seahorse XFe96 platform to generate bioenergetic profiles for the response to the bona-fide TLR2 and TLR4 ligands, FSL-1 and LPS respectively. Despite previous reports of species-specific differences in TLR signalling and cytokine production between human and bovine MØ, we observed similar respiratory profiles for both species. Basal respiration remained constant between stimulated MØ and controls, whereas addition of TLR ligands induced increased glycolysis. In contrast to MØ stimulation withM. tuberculosisPPD, another TLR2 ligand,M. bovisPPD treatment significantly enhanced basal respiration rates and glycolysis only in human MØ. Respiratory profiling further revealed significant elevation of ATP-linked OCR and maximal respiration suggesting a strong OXPHOS activation uponM. bovisPPD stimulation in human MØ. Our results provide an exploratory set of data elucidating the basic respiratory profile of bovine vs. human MØ that will not only lay the foundation for future studies to investigate host-tropism of theM. tuberculosiscomplex but may explain inflammatory differences observed for other zoonotic diseases.HighlightsSimilar baseline respiratory profiles for human and bovine macrophagesM. bovisPPD treatment altered metabolic profile only in human MØStrong OXPHOS activation uponM. bovisPPD stimulation only in human MØGraphical AbstractCreated with BioRender (www.biorender.com) by A. Gibson