bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inverse Material Parameter Estimation of Patient Specific Finite Element Models at the Carotid Bifurcation: The Impact of Excluding the Zero Pressure Configuration and Residual Stress
Authors: Johnston R. D , Ghasemi M. , Lally C. 
Published: April 2022

Abstract SummaryThe carotid bifurcation experiences a complex loading environment due to its anatomical structure. Previousin-vivomaterial parameter estimation methods often use simplified model geometries, isotropic hyperelastic constitutive equations or neglect key aspects of the vessel, such as the zero-pressure configuration or residual stress. These factors have independently been shown to alter the stress environment of the vessel wall. Characterising the location of high stress in the vessel wall has often been proposed as a potential indicator of structural weakness. However, excluding the afore-mentioned zero-pressure configuration, residual stress and patient specific material parameters can lead to an incorrect estimation of the true stress values observed, meaning stress alone as a risk indicator of rupture is insufficient. In this study, we investigate how the estimated material parameters and overall stress distributions in geometries of carotid bifurcations, extracted fromin-vivoMR images, alter with the inclusion of the zero-pressure configuration and residual stress.This approach consists of the following steps: (1) geometry segmentation and hexahedral meshing fromin-vivoMRI images at two known phases; (2) computation of the zero-pressure configuration and the associated residual stresses; (3) minimisation of an objective function built on the difference between the stress states of an “ almost true” stress field at two known phases and a “deformed” stress field by altering the input material parameters to determine patient specific material properties; and (4) comparison of the stress distributions throughout these carotid bifurcations for all cases with estimated material parameters. This numerical approach provides insights into the need for estimation of both the zero-pressure configuration and residual stress for accurate material property estimation and stress analysis for the carotid bifurcation, establishing the reliability of stress as a rupture risk metric.Graphical Abstract
Stably bound adaptor proteins modulate directionality of RNP transport
Authors: Phea Ly Jane , Ephrussi Anne 
Published: April 2022

AbstractKinesin-1 and cytoplasmic dynein are molecular motors that mediate long range transport of cargoes along the microtubule cytoskeleton. oskar RNA has been documented to switch between the motors during its localization in the Drosophila germline syncytium. oskar RNA undergoes dynein-mediated transport from the transcriptionally active nurse cells into the oocyte, following which the RNA translocates via kinesin to the posterior pole. Adaptor proteins link the RNA to its motors: the Egalitarian-Bicaudal-D complex links dynein to oskar RNA for the initial phase of transport, whereas atypical Tropomyosin 1 (aTm1) links kinesin-1 to oskar RNA for the latter phase. Components of the Exon Junction Complex (EJC) as well as the SOLE, a stem loop formed upon splicing of oskar RNA, have also been found to be necessary for kinesin-mediated transport of oskar RNA. In this study, to dissect the minimal elements required for kinesin-based transport, we tethered aTm1 or kinesin-1 to oskar RNA constructs lacking the SOLE. Our results suggest that stably bound aTm1 can indeed bypass the SOLE and EJC to mediate kinesin-1 activity, but the effects of tethered aTm1 are less potent than that of tethered kinesin-1. We also tethered Bicaudal-D to oskar RNA, to test whether this would affect kinesin-directed transport of oskar RNA, and found that tethered Bicaudal-D directs dynein mediated localization. Our results show that activated Bicaudal-D, along with the recruited dynein, is sufficient for dynein activity. We also show that stable binding of kinesin-1 to the RNA cargo is sufficient for strong kinesin-1 activity. Stably bound aTm1, meanwhile, can only mediate mild kinesin activity, suggesting that other factors may be required to stabilize the binding of kinesin-1 to the RNA cargo.
A systematic examination of learning in the invasive antLinepithema humilereveals very rapid development of short and long-term memory
Authors: Wagner Thomas , Galante Henrique , Josens Roxana , Czaczkes Tomer J. 
Published: April 2022

AbstractThe Argentine ant (Linepithema humile) is one of the most damaging and widespread invasive ant species worldwide. However, control attempts often fail due to bait rejection or insufficient bait uptake. Increasing preference for, and consumption of, bait is thus an important requirement for successful control. Learning and within-nest information transfer might be a potential tool for achieving this goal. We conducted a systematic investigation of olfactory learning and route learning in Argentine ants. The ants showed very strong and rapid route learning, choosing the correct arm in a Y-maze 65% of time after just one visit, and 84% correct after two. Odour learning was even more rapid, reaching up to 85% correct choices after just one exposure to flavoured food. Learning is long-lasting, with 73% correct choices after 48h. Food flavour information is transferred efficiently between nestmates in the nest, driving preference: naïve ants housed with ants fed on flavoured food show a strong preference (77%) for that odour after 24h. Overall,Linepithema humileare outstanding learners. This, coupled with efficient intranidal information transfer and strong pheromonal recruitment, may help explain their ability to discover and then dominate resources. However, these strengths could potentially be used against them, by exploiting learning and information transfer to increase toxic bait uptake. Steering ant preference by leveraging learning might be an underappreciated tool in invasive alien species control.
From individual behaviors to collective outcomes: fruiting body formation in Dictyostelium as a group-level phenotype
Authors: Kuzdzal-Fick Jennie F. , Moreno Armando , Broersma Cathleen M.E. , Cooper Tim F. , Ostrowski Elizabeth A. 
Published: April 2022

AbstractCollective phenotypes, which arise from the interactions among individuals, can be important for the evolution of higher levels of biological organization. However, how a group’s composition determines its collective phenotype remains poorly understood. When starved, cells of the social amoeba Dictyostelium discoideum cooperate to build a multicellular fruiting body, and the morphology of the fruiting body is likely advantageous to the surviving spores. We assessed how the number of strains, as well as their genetic and geographic relationships to one another, impact the group’s morphology and productivity. We find that some strains consistently enhance or detract from the productivity of their groups, regardless of the identity of the other group members. We also detect extensive pairwise and higher-order genotype interactions, which collectively have a large influence on the group phenotype. Whereas previous work in Dictyostelium has focused almost exclusively on whether spore production is equitable when strains cooperate to form multicellular fruiting bodies, our results suggest a previously unrecognized impact of chimeric co-development on the group phenotype. Our results demonstrate how interactions among members of a group influence collective phenotypes and how group phenotypes might in turn impact selection on the individual.
Proximal Exploration for Model-guided Protein Sequence Design
Authors: Ren Zhizhou , Li Jiahan , Ding Fan , Zhou Yuan , Ma Jianzhu , Peng Jian 
Published: April 2022

AbstractDesigning protein sequences with a particular biological function is a long-lasting challenge for protein engineering. Recent advances in machine-learning-guided approaches focus on building a surrogate sequence-function model to reduce the burden of expensive in-lab experiments. In this paper, we study the exploration mechanism of model-guided sequence design. We leverage a natural property of protein fitness landscape that a concise set of mutations upon the wild-type sequence are usually sufficient to enhance the desired function. By utilizing this property, we propose Proximal Exploration (PEX) algorithm that prioritizes the evolutionary search for high-fitness mutants with low mutation counts. In addition, we develop a specialized model architecture, called Mutation Factorization Network (MuFacNet), to predict low-order mutational effects, which further improves the sample efficiency of model-guided evolution. In experiments, we extensively evaluate our method on a suite of in-silico protein sequence design tasks and demonstrate substantial improvement over baseline algorithms.
Cryo-EM structure of an atypical proton-coupled peptide transporter: Di- and tripeptide permease C
Authors: Killer Maxime , Finocchio Giada , Mertens Haydyn D.T. , Svergun Dmitri I. , Pardon Els , Steyaert Jan , Löw Christian 
Published: April 2022

AbstractProton-coupled Oligopeptide Transporters (POTs) of the Major Facilitator Superfamily (MFS) mediate the uptake of short di- and tripeptides in all phyla of life. POTs are thought to constitute the most promiscuous class of MFS transporters, with the potential to transport more than 8400 unique substrates. Over the past two decades, transport assays and biophysical studies have shown that various orthologues and paralogues display differences in substrate selectivity. The E. coli genome codes for four different POTs, known as Di- and Tripeptide permeases A-D (DtpA-D). DtpC was shown previously to favor positively charged peptides as substrates. In this study, we describe, how we determined the structure of the 53 kDa DtpC by cryogenic electron microscopy (cryo-EM), and provide structural insights into the ligand specificity of this atypical POT. We collected and analyzed data on the transporter fused to split superfolder GFP (split sfGFP), in complex with a 52 kDa macrobody and with a 13 kDa nanobody. The latter sample was more stable, rigid and a significant fraction dimeric, allowing us to reconstruct a 3D volume of DtpC at a resolution of 2.7 Å. This work provides a molecular explanation for the selectivity of DtpC, and highlights the value of small and rigid fiducial markers such as nanobodies for structure determination of low molecular weight integral membrane proteins lacking soluble domains.
The SNARE Sec22b regulates phagosome maturation by promoting ORP8-mediated PI(4)P exchange at ER-phagosome contact sites
Authors: Santos Nina Criado , Bouvet Samuel , Bermont Flavien , Castelbou Cyril , Mansour Farah , Azam Maral , Giordano Francesca , Nunes-Hasler Paula 
Published: April 2022

AbstractThe precise control of phagosome maturation is critical for innate and adaptive immunity, determining whether phagocytosed material is destroyed or used to present antigens. We observed previously that non-fusogenic contacts between the endoplasmic reticulum (ER) and phagosomes, called membrane contact sites (MCS), are tethered by the calcium regulator STIM1 and fine-tune phagosomal maturation. The secretory pathway SNARE protein Sec22b has been implicated in controlling phagocytosis, phagosome maturation and antigen presentation, though its effects are controversial, and its mechanism of action poorly understood. Recently, Sec22b was shown to tether MCS at the plasma membrane without mediating membrane fusion. Here, we show that Sec22b localizes to and regulates the frequency of ER-phagosome contacts independently of STIM proteins. Sec22b knockdown and overexpression of a an MCS-disrupting mutant Sec22b-P33 induced only mild or no effect on global and local calcium signalling. However, Sec22b knockdown altered phagosomal phospholipids including PI(3)P, PI(4)P and PS, but not PI(4,5)P2. Increased PI(4)P in shSec22b cells was rescued by re-expression of Sec22b or the artificial MCS tether MAPPER but not the P33 mutant. Moreover, Sec22b co-precipitated and was co-recruited to phagosomes with the PS/PI(4)P lipid exchange protein ORP8. Expression of wild-type, but not mutant ORP8, also rescued phagosomal PI(4)P. Concordantly, Sec22b, MAPPER and ORP8 but not P33 or the ORP8 mutant decreased phagolysosome fusion in shSec22b cells. These results clarify a novel mechanism through which Sec22b controls phagosome maturation and beg a reassessment of the relative contribution of Sec22b-mediated fusion versus tethering to phagosome biology.
Model evolution in SARS-CoV-2 spike protein sequences using a generative neural network
Authors: Kumar Anup 
Published: April 2022

AbstractModelling evolutionary elements inherent in protein sequences, emerging from one clade into another of the SARS-CoV-2 virus, would provide insights to augment our understanding of its impact on public health and may help in formulating better strategies to contain its spread. Deep learning methods have been used to model protein sequences for SARS-CoV-2 viruses. A few significant drawbacks in these studies include being deficient in modelling end-to-end protein sequences, modelling only those genomic positions that show high activity and upsampling the number of sequences at each genomic position for balancing the frequency of mutations. To mitigate such drawbacks, the current approach uses a generative model, an encoder-decoder neural network, to learn the natural progression of spike protein sequences through adjacent clades of the phylogenetic tree of Nextstrain clades. Encoder transforms a set of spike protein sequences from the source clade (20A) into its latent representation. Decoder uses the latent representation, along with Gaussian distributed noise, to generate a different set of protein sequences that are closer to the target clade (20B). The source and target clades are adjacent nodes in the phylogenetic tree of different evolving clades of the SARS-CoV-2 virus. Sequences of amino acids are generated, for the entire length, at each genomic position using the latent representation of the amino acid generated at a previous step. Using trained models, protein sequences from the source clade are used to generate sequences that form a collection of evolved sequences belonging to all children clades of the source clade. A comparison of this predicted evolution (between source and generated sequences) of proteins with the true evolution (between source and target sequences) shows a high pearson correlation (> 0.7). Moreover, the distribution of the frequencies of substitutions per genomic position, including high- and low-frequency positions, in source-target sequences and source-generated sequences exhibit a high resemblance (pearson correlation > 0.7). In addition, the model partially predicts a few substitutions at specific genomic positions for the sequences of unseen clades (20J (Gamma)) where they show little activity during training. These outcomes show the potential of this approach in learning the latent mechanism of evolution of SARS-CoV-2 viral sequences.Codebasehttps://github.com/anuprulez/clade_prediction
Individual transcription factors modulate both the micromovement of chromatin and its long-range structure
Authors: Shaban Haitham A. , Friman Elias , Deluz Cédric , Tollenaere Armelle , Katanayeva Natalya , Suter David M. 
Published: April 2022

AbstractThe control of eukaryotic gene expression is intimately connected to highly dynamic chromatin structures. Gene regulation relies on activator and repressor transcription factors (TFs) that induce local chromatin opening and closing. However, it is unclear how nucleus-wide chromatin organization responds dynamically to the activity of specific TFs. Here we examined how two TFs with opposite effects on local chromatin accessibility modulate chromatin dynamics nucleus-wide. We combine High-resolution Diffusion mapping (Hi-D) and Dense Flow reConstruction and Correlation (DFCC) in living cells to obtain an imaging-based, nanometer-scale analysis of local diffusion processes and long-range coordinated movements of both chromatin and TFs. We show that the expression of either an individual transcriptional activator (CDX2) or repressor (SIX6) increases local chromatin mobility nucleus-wide, yet induces opposite coherent chromatin motions at the micron scale. Hi-C analysis of higher-order chromatin structures shows that induction of CDX2 leads to changes in local chromatin interactions and compartmentalization. These results thus document a close relation between chromatin dynamics on the microscale and changes in compartmental structures. Given that inhibition of transcription initiation and elongation by RNA Pol II have almost no impact on the global chromatin dynamics induced by CDX2, we suggest that CDX2 alters chromatin structures independently from transcription. Our biophysical analysis shows that sequence-specific TFs mobilize long-range chromatin structure on multiple levels, providing evidence that local chromatin changes brought about by TFs can alter both the dynamics and the long-range organization of chromatin in living cells.Significance statementIn eukaryotes, DNA is embedded into a higher-order structure called chromatin that varies between a closed state that is inaccessible to DNA-binding proteins, and an open state that allows the assembly of the transcriptional machinery on DNA. The state of chromatin is dynamic and locally controlled by sequence-specific transcription factors (TFs). How local chromatin opening and closing initiated by TFs alter long-range dynamics of chromatin structures is unknown. Here we combine two nucleus-wide live-imaging techniques, Hi-D and DFCC, along with Hi-C (genomic analysis technique) to quantify both local and global chromatin dynamics, then to correlate these dynamics to structural changes. Our quantitative analysis reveals a differential impact of TFs in shaping and mobilizing long-range chromatin structures in living cells.
Modulation of Arabidopsis growth by volatile organic compounds from a root-derived bacterial community
Authors: Türksoy Gözde Merve , Carron Réjane , Koprivova Anna , Kopriva Stanislav , Wippel Kathrin , Andersen Tonni Grube 
Published: April 2022

AbstractPlant roots are surrounded by fluctuating biotic and abiotic factors. The living component – the microbiota – is actively shaped by the plant and plays an important role in overall plant health. While it has been shown that specialized metabolites exuded from the plant are involved in shaping host interactions with the microbiota, it is unclear how underground volatile organic compounds (VOCs) influence this communication. This is especially true for root-associated bacteria which are known to release VOCs that can influence plant growth. Using a simplified synthetic bacterial community (SynCom) representing the phylogenetic diversity of bacteria in the root microbiome, we set out to characterize plant growth and defense metabolites when subjected to bacterial VOCs (bVOCs). Moreover, by profiling the SynCom community composition after co-cultivation with the plant, we explored how members of the community influenced each other in our growth setup. Our findings reveal that plant growth promotion can occur via VOCs from a bacterial SynCom, but that the plant response differs for individual community members. In addition, we find that bVOCs are able to repress chemical defense responses in the plant, possibly to facilitate colonization. By removing key species from the SynCom, we find that complex bacteria-bacteria interactions are likely to underlie this phenomenon, and that bVOC-induced modulation of plant responses in the rhizosphere may be an emergent property of bacterial communities rather than depending on individual species.
Machine learning-assisted fluoroscopy of bladder function in awake mice
Authors: De Bruyn Helene , Corthout Nikky , Munck Sebastian , Everaerts Wouter , Voets Thomas 
Published: April 2022

AbstractUnderstanding the lower urinary tract (LUT) and development of highly needed novel therapies to treat LUT disorders depends on accurate techniques to monitor LUT (dys)function in preclinical models. We recently developed videocystometry in rodents, which combines intravesical pressure measurements with X-ray-based fluoroscopy of the LUT, allowing the in vivo analysis of the process of urine storage and voiding with unprecedented detail. Videocystometry relies on the precise contrast-based determination of the bladder volume at high temporal resolution, which can readily be achieved in anesthetized or otherwise motion-restricted mice but not in awake and freely moving animals. To overcome this limitation, we developed a machine-learning method, in which we trained a neural network to automatically detect the bladder in fluoroscopic images, allowing the automatic analysis of bladder filling and voiding cycles based on large sets of time-lapse fluoroscopic images (>3 hours at 30 images/second) from behaving mice and in a non-invasive manner. With this approach, we found that urethane, an injectable anesthetic that is commonly used in preclinical urological research, has a profound, dose-dependent effect on urethral relaxation and voiding duration and that implantation of a suprapubic catheter, as is standardly performed for cystometric analyses, leads to a ∼4-fold reduction in bladder capacity. Our findings provide a paradigm for the non-invasive, in vivo monitoring of a hollow organ in behaving animals and pinpoint important limitations of the current gold standard techniques to study the LUT in mice.
An Inhibitory Function of TRPA1 Channels in TGF-β1-driven Fibroblast to Myofibroblast Differentiation
Authors: Geiger Fabienne , Zeitlmayr Sarah , Staab-Weijnitz Claudia A. , Rajan Suhasini , Breit Andreas , Gudermann Thomas , Dietrich Alexander 
Published: April 2022

AbstractTransient receptor potential ankyrin 1 (TRPA1) is a non-selective Ca2+ permeable cation channel, which was originally cloned from human lung fibroblasts (HLFs). TRPA1-mediated Ca2+ entry is evoked by exposure to several chemicals, including allyl isothiocyanate (AITC), and a protective effect of TRPA1 activation in the development of cardiac fibrosis has been proposed. Yet, the function of TRPA1 in transforming growth factor β1 (TGF-β1)-driven fibroblast to myofibroblast differentiation and the development of pulmonary fibrosis remains elusive. TRPA1 expression and function was analyzed in cultured primary HLFs, and mRNA levels were significantly reduced after adding TGF-β1. Expression of genes encoding fibrosis markers, e.g. alpha smooth muscle actin (ACTA2), plasminogen activator inhibitor 1 (SERPINE1), fibronectin (FN1) and type I collagen (COL1A1) was increased after siRNA-mediated down-regulation of TRPA1-mRNA in HLFs. Moreover, AITC-induced Ca2+ entry in HLFs was decreased after TGF-β1 treatment and by application of TRPA1 siRNAs, while AITC treatment alone did not reduce cell viability or enhanced apoptosis. Cell barrier function increased after addition of TRPA1 siRNAs or TGF-β1 treatment. Most interestingly, AITC-induced TRPA1 activation augmented ERK1/2 phosphorylation, which might inhibit TGF-β-receptor signaling. Our results suggest an inhibitory function of TRPA1 channels in TGF-β1-driven fibroblast to myofibroblast differentiation. Therefore, activation of TRPA1 channels might be protective during the development of pulmonary fibrosis in patients.