bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whose energy cost would birds like to save? a revisit of the migratory formation flight
Authors: Shi Mingming , Ransquin Ignace , Chatelain Philippe , Hendrickx Julien M. 
Published: March 2023

AbstractLine formation of migrating birds is well-accepted to be caused by birds exploiting wake benefits to save energy expenditure. A flying bird generates wingtip trailing vortices that stir the surrounding air upward and downward, and the following bird can get a free supportive lift when positioned at the upward airflow region. However, little to no attention has been paid to clarifying birds’ interests in energy saving, namely, do birds intend to reduce their individual energy consumption or the total energy of the flock? Here, by explicitly considering birds’ interests, we employ a modified fixed-wing wake model that includes the wake dissipation to numerically reexamine the energy saving mechanism in line formation. Surprisingly, our computations show that line formation cannot be explained simply by energy optimization. This remains true whether birds are selfish or cooperative. However, line formations may be explained by strategies optimizing energy cost and either avoiding collision or maintaining vision comfort. We also find that the total wake benefit of the formation attained by selfish birds does not differ much from that got by cooperative birds, the maximum that birds can attain. This implies that selfish birds are still able to fly in formation with very high efficiency of energy saving. In addition, we explore the hypothesis that birds are empathetic and would like to optimize their own energy cost and the neighbors’. Our analysis shows that if birds are more empathetic, the resulting line formation shape deviates more from a straight line, and the flock enjoys higher total wake benefit.Author summaryMigratory birds can achieve remarkable performance and efficiency in energy exploitation during annual round-trip migration flight. Theoretical and experimental results have shown that this might be achieved because birds fly together in formation with specific shapes, e.g. the noticeable V formation, to utilize the aerodynamic benefits generated by their flock mates. However, it is still unclear whether energy-guided behavior indeed can lead to these formations. We show that the special formation adopted by migratory birds cannot be explained purely by the energy exploitation mechanism, and that birds’ vision performance and collision avoidance very likely also play important roles in the formation emergence. Our results imply that birds fly together in formation because of energy saving, but the specific shape of the formation depends on non-aerodynamic reasons. The research provides further understandings of the emergence of migratory formation and the energy saving mechanism of animal groups. It may also indicate that wing flapping, currently not considered, has an important effect on the way birds exploit aerodynamic benefits from others during the formation flight.
Determinants of genetic diversity in sticklebacks
Authors: Kivikoski Mikko , Feng Xueyun , Löytynoja Ari , Momigliano Paolo , Merilä Juha 
Published: March 2023

AbstractUnderstanding what determines species and population differences in levels of genetic diversity has important implications for our understanding of evolution, as well as for the conservation and management of wild populations. Previous comparative studies have emphasized the roles of linked selection, life-history trait variation and genomic properties, rather than pure demography, as important determinants of genetic diversity. However, these findings are based on coarse estimates across a range of highly diverged taxa, and it is unclear how well they represent the processes within individual species. We assessed genome-wide genetic diversity (π) in 45 nine-spined stickleback (Pungitius pungitius) populations and found thatπvaried 15-fold among populations (πmin≈0.00015,πmax≈0.0023) whereas estimates of recent effective population sizes varied 122-fold. Analysis of inbreeding coefficients (FROH) estimated from runs of homozygosity revealed strong negative association betweenπand FROH. Genetic diversity was also negatively correlated with mean body size and longevity, but these associations were not statistically significant after controlling for demographic effects (FROH). The results give strong support for the view that populations’ demographic features, rather than life history differences, are the chief determinants of genetic diversity in the wild.
The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in colon cancer cells
Authors: Slaninová Věra , Heron-Milhavet Lisa , Robin Mathilde , Jeanson Laura , Kantar Diala , Tosi Diego , Bréhélin Laurent , Gongora Céline , Djiane Alexandre 
Published: March 2023

SUMMARYYAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the P73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. Using several colorectal cancer cell lines, we show here that oxaliplatin treatment led to a dramatic core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of P73, but which required the nuclear relocalization of TAZ. Accordingly, Verteporfin and CA3, two drugs affecting the activity of YAP and TAZ, showed an antagonistic with oxaliplatin in co-treatments. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and P53 activity pushes cells towards apoptosis.
A primer-independent DNA polymerase-based method for competent whole-genome amplification of intermediate to high GC sequences
Authors: Ordóñez Carlos D. , Mayoral-Campos Carmen , Egas Conceição , Redrejo-Rodríguez Modesto 
Published: March 2023

AbstractMultiple displacement amplification (MDA) has proven to be a useful technique for obtaining large amounts of DNA from tiny samples in genomics and metagenomics. However, MDA has limitations, such as amplification artifacts and biases that can interfere with subsequent quantitative analysis. To overcome these challenges, alternative methods and engineered DNA polymerase variants have been developed. Here, we present new MDA protocols based on the primer-independent DNA polymerase (piPolB), a replicative-like DNA polymerase endowed with DNA priming and proofreading capacities. These new methods were tested on a genomes mixture containing diverse sequences with high-GC content, followed by deep sequencing. Protocols relying on piPolB as a single enzyme cannot achieve competent amplification due to its limited processivity and the presence ofab initioDNA synthesis. However, an alternative method called piMDA, which combines piPolB with Φ29 DNA polymerases, allows proficient and faithful amplification of the genomes. In addition, the prior denaturation step commonly performed in MDA protocols is dispensable, resulting in a more straightforward protocol. In summary, piMDA outperforms commercial methods in the amplification of metagenomes containing high GC sequences and exhibits similar profiling, error rate, and variant determination as the non-amplified samples.Graphical abstractSchematic representation of methods based on multiple displacement amplification (MDA) for whole genome amplification. The diagrams above represent protocols initiated by random primers (RP-MDA) or a DNA primase-generated short DNA primers (PrimPol-MDA) and continued by Φ29DNAP, whereas the schematics below show piPolB-mediated MDA (left) and the piMDA protocol (right), in which piPolB synthesizes DNA strands that are further extended by Φ29DNAP.
Increased drought resistance in state transition mutants is linked to modified plastoquinone pool redox state
Authors: Leverne Lucas , Roach Thomas , Perreau François , Maignan Fabienne , Krieger-Liszkay Anja 
Published: March 2023

AbstractIdentifying traits that exhibit improved drought resistance is highly important to cope with the challenges of predicted climate change. We investigated the response of state transition mutants to drought. Compared with the wild type, state transition mutants were less affected by drought. Photosynthetic parameters in leaves probed by chlorophyll fluorescence confirmed that mutants possess a more reduced plastoquinone (PQ) pool, as expected due to the absence of state transitions. Seedlings of the mutants showed an enhanced growth of the primary root and more lateral root formation. The photosystem II inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea, leading to an oxidized PQ pool, inhibited primary root growth in wild type and mutants, while the cytochromeb6fcomplex inhibitor 2,5-dibromo-3-methyl-6-isopropylbenzoquinone, leading to a reduced PQ pool, stimulated root growth. A more reduced state of the PQ pool was associated with a slight but significant increase in singlet oxygen production. Singlet oxygen may trigger a, yet unknown, signaling cascade promoting root growth. We propose that photosynthetic mutants with a deregulated ratio of photosystem II to photosystem I activity can provide a novel path for improving crop drought resistance.Summary StatementArabidopsis thalianamutants affected in state transitions are more drought resistant.
Antibodies generatedin vitroandin vivoelucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine
Authors: Buzas Dora , Bunzel H Adrian , Staufer Oskar , Milodowski Emily J , Edmunds Grace L , Bufton Joshua C , Vidana Mateo Beatriz V , Yadav Sathish K N , Gupta Kapil , Fletcher Charlotte , Kavanagh Williamson Maia , Harrison Alexandra , Borucu Ufuk , Capin Julien , Francis Ore , Balchin Georgia , Hall Sophie , Vivoli Vega Mirella , Durbesson Fabien , Vincentelli Renaud , Roe Joe , Wooldridge Linda , Burt Rachel , Anderson J L Ross , Mulholland Adrian J ,   Bristol UNCOVER Group, Hare Jonathan , Bailey Mick , Davidson Andrew D , Finn Adam , Morgan David , Mann Jamie , Spatz Joachim , Garzoni Frederic , Schaffitzel Christiane , Berger Imre 
Published: March 2023

AbstractCOVID-19 continues to damage populations, communities and economies worldwide. Vaccines have reduced COVID-19-related hospitalisations and deaths, primarily in developed countries. Persisting infection rates, and highly transmissible SARS-CoV-2 Variants of Concern (VOCs) causing repeat and breakthrough infections, underscore the ongoing need for new treatments to achieve a global solution. Based on ADDomer, a self-assembling protein nanoparticle scaffold, we created ADDoCoV, a thermostable COVID-19 candidate vaccine displaying multiple copies of a SARS-CoV-2 receptor binding motif (RBM)-derived epitope.In vitrogenerated neutralising nanobodies combined with molecular dynamics (MD) simulations and electron cryo-microscopy (cryo-EM) established authenticity and accessibility of the epitopes displayed. A Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Antibodies generated by immunising mice cross-reacted with VOCs including Delta and Omicron. Our study elucidates nasal administration of ADDomer-based nanoparticles for active and passive immunisation against SARS-CoV-2 and provides a blueprint for designing nanoparticle reagents to combat respiratory viral infections.
CRISPR/Cas9-mediated knockout of the ubiquitin variant UbKEKSreveals a role in regulating nucleolar structures and composition
Authors: Frion Julie , Meller Anna , Marbach Gwendoline , Lévesque Dominique , Roucou Xavier , Boisvert François-Michel 
Published: March 2023

AbstractUbiquitination is a post-translational modification responsible for one of the most complex multi-layered communication and regulation system in the cell. Over the past decades, new ubiquitin variants and ubiquitin-like proteins arose to further enrich this mechanism. Among them, the recently discovered ubiquitin variant UbKEKScan specifically target several proteins and yet, functional consequences of this new modification remain unknown. The absence of UbKEKSinduces accumulation of lamin A in the nucleoli, highlighting the need for deeper investigations about protein composition and functions regulation of this highly dynamic and membrane-less compartment. By using data independent acquisition mass spectrometry and microscopy, we show here that despite not impacting protein stability, UbKEKSis required to maintain normal nucleolar organization. The absence of UbKEKSincreases nucleoli’s size and accentuate their circularity while disrupting dense fibrillar component and fibrillar center structures. Moreover, depletion of UbKEKSleads to distinct changes in nucleolar composition. Notably, lack of UbKEKSfavors nucleolar sequestration of known apoptotic regulators such as IFI16 or p14ARF, resulting in an increase of apoptosis in UbKEKSknockout cells observed by flow cytometry and real-time cellular growth monitoring. Overall, the results presented here identifies the first cellular functions of the UbKEKSvariant and lay the foundation stone to establish UbKEKSas a new universal layer of regulation in the already complex ubiquitination system.
Dissecting muscle synergies in the task space
Authors: Reilly David Ó’ , Delis Ioannis 
Published: March 2023

AbstractThe muscle synergy is a guiding concept in motor control research that relies on the general notion of muscles ‘working together’towards task performance. However, although the synergy concept has provided valuable insights into motor coordination, muscle interactions have not been fully characterised with respect to task performance. Here, we address this research gap by proposing a novel perspective to the muscle synergy that assigns specific functional roles to muscle couplings by characterising their task-relevance. Our novel perspective provides nuance to the muscle synergy concept, demonstrating how muscular interactions can ‘work together’in different ways: a) irrespective of the task at hand but also b) redundantly or c) complementarily towards common task-goals. To establish this perspective, we leverage information- and network-theory and dimensionality reduction methods to include discrete and continuous task parameters directly during muscle synergy extraction. Specifically, we introduce co-information as a measure of the task relevance of muscle interactions and use it to categorise such interactions as task-irrelevant (present across tasks), redundant (shared task information) or synergistic (different task information). To demonstrate these types of interactions in real data, we firstly apply the framework in a simple way, revealing its added functional and physiological relevance with respect to current approaches. We then apply the framework to large-scale datasets and extract generalizable and scale-invariant representations consisting of subnetworks of synchronised muscle couplings and distinct temporal patterns. The representations effectively capture the functional interplay between task end-goals and biomechanical affordances and the concurrent processing of functionally similar and complementary task information. The proposed framework unifies the capabilities of current approaches in capturing distinct motor features while providing novel insights and research opportunities through a nuanced perspective to the muscle synergy.
Creation of Advance Construction of CRISPR-Cas9 via using Multi Round Gateway Cloning
Authors: Jameel M. Rizwan 
Published: March 2023

ABSTRACTCRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated system) is used to edit specific genomic sequences with precision and efficacy. CRISPR/Cas9 system mediated double strand binding site through error-prone non homologous end joining repair in targeted sequences, which the deletion or insertion can be achieved by knock out gene. Creation advance construct of CRISPR/Cas9 of soluble starch synthase II-1, 2 and 3 (SSSII) genes in single destination binary vector through multi round LR reaction of Gateway technology. Gateway cloning system developed the suitable for the site-specific DNA recombination of lambda-bacteriophage andccdBthe cytotoxic protein, which is poisonous to most E. coli strains. A genetic transformation vector designed with appropriate gRNAs, Cas9, and antibiotic resistance was used to create SSSII knockout mutants.
Uncovering the Morphological Evolution of Language-Relevant Brain Areas
Authors: Gallardo Guillermo , Eichner Cornelius , Sherwood Chet C. , Hopkins William D. , Anwander Alfred , Friederici Angela D. 
Published: March 2023

AbstractHuman language is supported by a cortical network involving Broca’s area which comprises Brodmann Areas 44 and 45 (BA44, BA45). While cytoarchitectonic homolog areas have been identified in nonhuman primates, it remains unknown how these regions evolved to support human language. Here, we use histological data and advanced cortical registration methods to precisely compare the morphology of BA44 and 45 between humans and chimpanzees. We found a general expansion of Broca’s areas in humans, with the left BA44 enlarging the most, growing anteriorly into a region known to process syntax. Together with recent functional studies, our findings show that BA44 evolved from a purely action-related region to a more expanded region in humans, with a posterior portion supporting action and an anterior portion supporting syntactic processes. Furthermore, our findings provide a solution for the longstanding debate concerning the structural and functional evolution of Broca’s area and its role in action and language.
Magnipore: Prediction of differential single nucleotide changes in the Oxford Nanopore Technologies sequencing signal of SARS-CoV-2 samples
Authors: Spangenberg Jannes , zu Siederdissen Christian Höner , Žarković Milena , Triebel Sandra , Rose Ruben , Christophersen Christina Martínez , Paltzow Lea , Hegab Mohsen M. , Wansorra Anna , Srivastava Akash , Krumbholz Andi , Marz Manja 
Published: March 2023

AbstractOxford Nanopore Technologies (ONT) allows direct sequencing of ribonucleic acids (RNA) and, in addition, detection of possible RNA modifications due to deviations from the expected ONT signal. The software available so far for this purpose can only detect a small number of modifications. Alternatively, two samples can be compared for different RNA modifications. We presentMagnipore, a novel tool to search for significant signal shifts between samples of Oxford Nanopore data from similar or related species.Magniporeclassifies them into mutations and potential modifications. We useMagniporeto compare SARS-CoV-2 samples. Included were representatives of the early 2020s Pango lineages (n=6), samples from Pango lineages B.1.1.7 (n=2, Alpha), B.1.617.2 (n=1, Delta), and B.1.529 (n=7, Omicron).Magniporeutilizes position-wise Gaussian distribution models and a comprehensible significance threshold to find differential signals. In the case of Alpha and Delta,Magniporeidentifies 55 detected mutations and 15 sites that hint at differential modifications. We predicted potential virus-variant and variant-group-specific differential modifications.Magniporecontributes to advancing RNA modification analysis in the context of viruses and virus variants.
CLN3 deficiency leads to neurological and metabolic perturbations during early development
Authors: Heins-Marroquin Ursula , Singh Randolph R. , Perathoner Simon , Gavotto Floriane , Ruiz Carla Merino , Patraskaki Myrto , Gomez-Giro Gemma , Borgmann Felix Kleine , Meyer Melanie , Carpentier Anaïs , Warmoes Marc O. , Jäger Christian , Mittelbronn Michel , Schwamborn Jens C. , Cordero-Maldonado Maria Lorena , Crawford Alexander D. , L. Schymanski Emma , Linster Carole 
Published: March 2023

AbstractJuvenile Neuronal Ceroid Lipofuscinosis (or Batten disease) is an autosomal recessive, rare neurodegenerative disorder that affects mainly children above the age of 5 years and is most commonly caused by mutations in the highly conservedCLN3gene. Here, we generatedcln3morphants and stable mutant lines in zebrafish. Although neither morphant nor mutantcln3larvae showed any obvious developmental or morphological defects, behavioral phenotyping of the mutant larvae revealed higher basal activity, hyposensitivity to abrupt light changes and hypersensitivity to pro-convulsive drugs. Importantly, in-depth metabolomics and lipidomics analyses revealed significant accumulation of several glycerophosphodiesters (GPDs) and a global decrease of bis(monoacylglycero)phosphate (BMP) species, two classes of molecules previously proposed as potential biomarkers forCLN3disease based on independent studies in other organisms. We could also demonstrate GPD accumulation in human-induced pluripotent stem cell-derived cerebral organoids carrying a pathogenic variant forCLN3. Our models revealed that GPDs accumulate at very early stages of life in the absence of functional CLN3 and highlight glycerophosphoinositol and BMP as promising biomarker candidates for pre-symptomaticCLN3disease.
Where and when local adaptation happens: lessons from the European barn owl (Tyto alba)
Authors: Corval Hugo , Cumer Tristan , Topaloudis Alexandros , Roulin Alexandre , Goudet Jérôme 
Published: March 2023

AbstractClimatic variations subject living species to evolutionary stresses and shape their distributions. Since the Last Glacial Maximum (LGM) and the subsequent temperature rise, species (re-) colonised higher latitudes. Among the evolutionary mechanisms involved during this process, local adaptation is thought to be one of the keystones of species persistence. However, its relative role and location in space remain elusive. The Western Palearctic barn owl (Tyto alba) recolonised Europe after the LGM (from the Italian and Iberic peninsulas) and offers an excellent opportunity to study local adaptation at the continental scale. Here, we modelled the evolution of the barn owl’s ecological niche since LGM and showed that the birds probably followed its shift towards the North during the recolonisation. To identify traces of local adaptation, we scanned the entire genomes of 74 owls from 9 European populations using both Tajima’s D and population-specific FST and associated genomic variants to temperature and precipitation through a Redundancy analysis. The combination of these methods yielded a total of 394 genomic windows putatively involved in the local adaptation distributed over all populations. Interestingly, our results identified a large region under selection in both refugial populations, consistent with climate change and ecological convergence in the two peninsulas. This study shed light on the genomic basis of local adaptation of the European barn owl, emphasised the importance of considering the ecological niche as a dynamic entity and paved the way to a better understanding of where and how local adaptation happens in a context of postglacial recolonisation.