bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recognition of natural objects in the archerfish
Authors: Volotsky Svetlana , Ben-Shahar Ohad , Donchin Opher , Segev Ronen 
Published: August 2021

AbstractRecognition of individual objects and their categorization is a complex computational task. Nevertheless, visual systems are able to perform this task in a rapid and accurate manner. Humans and other animals can efficiently recognize objects despite countless variations in their projection on the retina due to different viewing angles, distance, illumination conditions, and other parameters. Numerous studies conducted in mammals have associated the recognition process with cortical activity. Although the ability to recognize objects is not limited to mammals and has been well-documented in other vertebrates that lack a cortex, the mechanism remains elusive. To address this gap, we explored object recognition in the archerfish, which lack a fully developed cortex. Archerfish hunt by shooting a jet of water at aerial targets. We leveraged this unique skill to monitor visual behavior in archerfish by presenting fish with a set of images on a computer screen above the water tank and observing the behavioral response. This methodology served to characterize the ability of the archerfish to perform ecologically relevant recognition of natural objects. We found that archerfish can recognize an individual object presented under different conditions and that they can also categorize novel objects into known categories. Manipulating features of these objects revealed that the fish were more sensitive to object contours than texture and that a small number of features was sufficient for categorization. Our findings suggest the existence of a complex visual process in the archerfish visual system that enables object recognition and categorization.
On co-activation pattern analysis and non-stationarity of resting brain activity
Authors: Matsui Teppei , Pham Trung Quang , Jimura Koji , Chikazoe Junichi 
Published: August 2021

AbstractThe non-stationarity of resting-state brain activity has received increasing attention in recent years. Functional connectivity (FC) analysis with short sliding windows and coactivation pattern (CAP) analysis are two widely used methods for assessing the dynamic characteristics of brain activity observed with functional magnetic resonance imaging (fMRI). However, the statistical nature of the dynamics captured by these techniques needs to be verified. In this study, we found that the results of CAP analysis were similar for real fMRI data and simulated stationary data with matching covariance structures and spectral contents. We also found that, for both the real and simulated data, CAPs were clustered into spatially heterogeneous modules. Moreover, for each of the modules in the real data, a spatially similar module was found in the simulated data. The present results suggest that care needs to be taken when interpreting observations drawn from CAP analysis as it does not necessarily reflect non-stationarity or a mixture of states in resting brain activity.HighlightsCAP was conducted for real fMRI data and a stationary null model.The results of CAP analysis were similar for the real and simulated data.Similar results for real and simulated data in both ROI- and voxel-based analyses.Results of CAP analysis may not reflect non-stationarity of resting brain activity.
Translation of MT-ATP6 pathogenic variants reveals distinct regulatory consequences from the co-translational quality control of mitochondrial protein synthesis
Authors: Ng Kah Ying , Richter Uwe , Jackson Christopher B. , Seneca Sara , Battersby Brendan J. 
Published: August 2021

AbstractPathogenic variants that disrupt human mitochondrial protein synthesis are associated with a clinically heterogenous group of diseases. Despite an impairment in oxidative phosphorylation being a common phenotype, the underlying molecular pathogenesis is more complex than simply a bioenergetic deficiency. Currently, we have limited mechanistic understanding on the scope by which a primary defect in mitochondrial protein synthesis contributes to organelle dysfunction. Since the proteins encoded in the mitochondrial genome are hydrophobic and need co-translational insertion into a lipid bilayer, responsive quality control mechanisms are required to resolve aberrations that arise with the synthesis of truncated and misfolded proteins. Here, we show that defects in the OXA1L-mediated insertion of MT-ATP6 nascent chains into the mitochondrial inner membrane are rapidly resolved by the AFG3L2 protease complex. Using pathogenic MT-ATP6 variants, we then reveal discrete steps in this quality control mechanism and the differential functional consequences to mitochondrial gene expression. The inherent ability of a given cell type to recognize and resolve impairments in mitochondrial protein synthesis may in part contribute at the molecular level to the wide clinical spectrum of these disorders.
Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish
Authors: Qi Jialing , Rittershaus Annegret , Priya Rashmi , Mansingh Shivani , Stainier Didier Y.R. , Helker Christian S.M. 
Published: August 2021

AbstractDuring cardiac development, endocardial cells (EdCs) produce growth factors to promote myocardial morphogenesis and growth. In particular, EdCs produce Neuregulin which is required for ventricular cardiomyocytes (CMs) to seed the multicellular ridges known as trabeculae. Defects in Neuregulin signaling, or in endocardial sprouting towards CMs, cause hypotrabeculation. However, the mechanisms underlying endocardial sprouting remain largely unknown. Here, we first show by live imaging in zebrafish embryos that EdCs interact with CMs via dynamic membrane protrusions. After touching CMs, these protrusions remain in close contact with their target despite the vigorous cardiac contractions. Loss of the CM-derived peptide Apelin, or of the Apelin receptor, which is expressed in EdCs, leads to reduced endocardial sprouting and hypotrabeculation. Mechanistically, Neuregulin signaling requires endocardial protrusions to activate extracellular signal-regulated kinase (Erk) signaling in CMs and trigger their delamination. Altogether, these data show that Apelin signaling dependent endocardial protrusions modulate CM behavior during trabeculation.
Influenza A virus (H1N1) infection induces microglia activation and temporal dysbalance in glutamatergic synaptic transmission
Authors: Düsedau Henning Peter , Steffen Johannes , Figueiredo Caio Andreeta , Boehme Julia Désirée , Schultz Kristin , Erck Christian , Korte Martin , Faber-Zuschratter Heidi , Smalla Karl-Heinz , Dieterich Daniela , Kröger Andrea , Bruder Dunja , Dunay Ildiko Rita 
Published: August 2021

3.AbstractInfluenza A virus (IAV) causes respiratory tract disease and is responsible for seasonal and reoccurring epidemics affecting all age groups. Next to typical disease symptoms such as fever and fatigue, IAV infection has been associated with behavioral alterations presumably contributing to the development of major depression. Previous experiments using IAV/H1N1 infection models have shown impaired hippocampal neuronal morphology and cognitive abilities, but the underlying pathways have not been fully described. In this study, we demonstrate that infection with a low dose non-neurotrophic H1N1 strain of IAV causes ample peripheral immune response followed by a temporary blood-brain-barrier disturbance. Although histological examination did not reveal obvious pathological processes in the brains of IAV-infected mice, detailed multidimensional flow cytometric characterization of immune cells uncovered subtle alterations in the activation status of microglia cells. More specifically, we detected an altered expression pattern of major histocompatibility complex class I and II, CD80, and F4/80 accompanied by elevated mRNA levels of CD36, CD68, C1QA, and C3, suggesting evolved synaptic pruning. To closer evaluate how these profound changes affect synaptic balance, we established a highly sensitive multiplex flow cytometry-based approach called Flow Synaptometry. The introduction of this novel technique enabled us to simultaneously quantify the abundance of pre- and postsynapses from distinct brain regions. Our data reveal a significant reduction of VGLUT1 in excitatory presynaptic terminals in the Cortex and Hippocampus, identifying a subtle dysbalance in glutamatergic synapse transmission upon H1N1 infection in mice. In conclusion, our results highlight the consequences of systemic IAV-triggered inflammation on the central nervous system and the induction and progression of neuronal alterations.
A novel effective live-attenuated human metapneumovirus vaccine candidate produced in the serum-free suspension DuckCelt®-T17 cell platform
Authors: Chupin Caroline , Pizzorno Andrés , Traversier Aurélien , Brun Pauline , Ogonczyk-Makowska Daniela , Padey Blandine , Milesi Cédrine , Dulière Victoria , Laurent Emilie , Julien Thomas , Galloux Marie , Lina Bruno , Eléouët Jean-François , Moreau Karen , Hamelin Marie-Eve , Terrier Olivier , Boivin Guy , Dubois Julia , Rosa-Calatrava Manuel 
Published: August 2021

AbstractHuman metapneumovirus (HMPV) is a major pediatric respiratory pathogen for which there is currently no specific treatment or licensed vaccine. Different strategies have been evaluated to prevent this infection, including the use of live-attenuated vaccines (LAVs). However, further development of LAV approaches is often hampered by the lack of highly efficient and scalable cell-based production systems that support worldwide vaccine production. In this context, avian cell lines cultivated in suspension are currently competing with traditional cell platforms used for viral vaccine manufacturing. We investigated whether the DuckCelt®-T17 avian cell line (Vaxxel) we previously described as an efficient production system for several influenza strains could also be used to produce a new HMPV LAV candidate (Metavac®), an engineered SH gene-deleted mutant of the A1/C-85473 strain of HMPV. To that end, we characterized the operational parameters of multiplicity of infection (MOI), cell density, and trypsin addition to achieve optimal production of the LAV Metavac® in the DuckCelt®-T17 cell line platform. We demonstrated that the DuckCelt®-T17 cell line is permissive and is well adapted to the production of the wild-type A1/C-85473 HMPV and the Metavac® vaccine candidate. Moreover, our results confirmed that the LAV candidate produced in DuckCelt®-T17 cells conserves its advantageous replication properties in LLC-MK2 and 3D-reconstituted human airway epithelium models, as well as its capacity to induce efficient neutralizing antibodies in a mouse model. Our results suggest that the DuckCelt®-T17 avian cell line is a very promising platform for scalable in-suspension serum-free production of the HMPV-based LAV candidate Metavac®.
Exploring the conformational landscape and stability of Aurora A using ion-mobility mass spectrometry and molecular modelling
Authors: Tomlinson Lauren J. , Batchelor Matthew , Sarsby Joscelyn , Byrne Dominic P. , Brownridge Philip , Bayliss Richard , Eyers Patrick A. , Eyers Claire E. 
Published: August 2021

ABSTRACTProtein kinase inhibitors are proving highly effective in helping treat a number of non-communicable diseases driven by aberrant kinase signaling. They are also extremely valuable as chemical tools to help delineate cellular roles of kinase signaling complexes. The binding of small molecule inhibitors induces conformational effects on kinase dynamics; evaluating the effect of such interactions can assist in developing specific inhibitors and is deemed imperative to understand both inhibition and resistance mechanisms. Using gas-phase ion mobility-mass spectrometry (IM-MS) we characterized changes in the conformational landscape and stability of the protein kinase Aurora A (Aur A) driven by binding of the physiological activator TPX2 or small molecule inhibition. Aided by molecular modeling, we establish three major conformations: one highly-populated compact conformer similar to that observed in most crystal structures, a second highly-populated conformer possessing a more open structure that is infrequently found in crystal structures, and an additional low-abundance conformer not currently represented in the protein databank. Comparison of active (phosphorylated) and inactive (non-phosphorylated) forms of Aur A revealed that the active enzyme has different conformer weightings and is less stable than the inactive enzyme. Notably, inhibitor binding shifts conformer balance towards the more compact configurations adopted by the unbound enzyme, with both IM-MS and modelling revealing inhibitor-mediated stabilisation of active Aur A. These data highlight the power of IM-MS in combination with molecular dynamics simulations to probe and compare protein kinase structural dynamics that arise due to differences in activity and as a result of compound binding.
NetRAX: Accurate and Fast Maximum Likelihood Phylogenetic Network Inference⋆
Authors: Lutteropp Sarah , Scornavacca Céline , Kozlov Alexey M. , Morel Benoit , Stamatakis Alexandros 
Published: August 2021

AbstractPhylogenetic networks are used to represent non-treelike evolutionary scenarios. Current, actively developed approaches for phylogenetic network inference jointly account for non-treelike evolution and incomplete lineage sorting (ILS). Unfortunately, this induces a very high computational complexity. Hence, current tools can only analyze small data sets.We present NetRAX, a tool for maximum likelihood inference of phylogenetic networks in the absence of incomplete lineage sorting. Our tool leverages state-of-the-art methods for efficiently computing the phylogenetic likelihood function on trees, and extends them to phylogenetic networks via the notion of “displayed trees”. NetRAX can infer maximum likelihood phylogenetic networks from partitioned multiple sequence alignments and returns the inferred networks in Extended Newick format.On simulated data, our results show a very low relative difference in BIC score and a near-zero unrooted softwired cluster distance to the true, simulated networks. With NetRAX, a network inference on a partitioned alignment with 8, 000 sites, 30 taxa, and 3 reticulations completes within a few minutes on a standard laptop.Our implementation is available under the GNU General Public License v3.0 at https://github.com/lutteropp/NetRAX.
The beneficial role ofCandida intermediaandSaccharomyces boulardiiyeasts on the immune response of mice vaccinated with a SARS-CoV-2 experimental vaccine
Authors: Piraine Renan Eugênio Araujo , Conrad Neida Lucia , Gonçalves Vitória Sequeira , Ramos Jeferson Vidart , Leite Fábio Pereira Leivas 
Published: August 2021

AbstractNon-Saccharomycesyeasts emerge as possible new probiotics with a beneficial effect equal to or greater than the reference probiotic yeast,Saccharomyces boulardii. In this work, we evaluated the immunomodulation effect caused byCandida intermediain mice vaccinated with inactivated SARS-CoV-2. We conducted preliminary tests using murine macrophages (RAW 264.7) stimulated with viable and heat-killed yeast cells, culture supernatant, and DNA, using qPCR to detect the mRNA transcription. Next, mice were supplemented withC. intermediabefore each dose of the SARS-CoV-2 vaccine, and then antibody production was measured by ELISA. The probiotic strainS. boulardiiCNCM I-745 was used as a control. We also explored the differences in fecal microbiomes between the non-supplemented and supplemented groups. Live cells ofC. intermediaincreased the transcription ofIL-4,IL-13, andSTAT3by macrophages RAW 264.7, while heat-killed cells up-regulatedTNFαandBcl6, and the culture supernatant positively impactedTLR2transcription. Concanavalin, zymosan, and lipopolysaccharide were used to stimulate splenocytes fromC. intermedia-supplemented animals, which showed increased transcription ofTNFα,IFNγ,IL-4,Bcl6, andSTAT3. Sera from these animals showed enhanced levels of anti-SARS-CoV-2 IgG, as well as IgG1 and IgM isotypes, and sIgA in fecal samples. The microbiome of theC. intermedia-supplemented group showed a higher abundance ofBacteroidesspp. andClostridiumspp., impacting the Bacteroidetes/Firmicutes balance. We concluded thatC. intermediaandS. boulardiicould stimulate and impact the gene expression of cells important for innate immunity, influence the composition of the gastrointestinal microbiome, and primarily boost the humoral response after vaccination.Statements and Declarations FundingThe present work was carried out with the support of Conselho Nacional de Desenvolvimento Científico (CNPq, Brazil), grant number 150538/2021-9.
The male and female gonad transcriptome of the edible sea urchin, Paracentrotus lividus: identification of sex-related and lipid biosynthesis genes
Authors: Machado André M. , Fernández-Boo Sergio , Nande Manuel , Pinto Rui , Costas Benjamin , Castro L. Filipe C. 
Published: August 2021

AbstractParacentrotus lividus is the most abundant, distributed and desirable echinoid species in Europe. Although, economically important, this species has scarce genomic resources available. Here, we produced and comprehensively characterized the male and female gonad transcriptome of P. lividus. The P. lividus transcriptome assembly has 53,865 transcripts, an N50 transcript length of 1,842 bp and an estimated gene completeness of 97.4% and 95.6% in Eukaryota and Metazoa BUSCO databases, respectively. Differential gene expression analyses yielded a total of 3371 and 3351 up regulated genes in P. lividus male and female gonad tissues, respectively. Additionally, we analysed and validated a catalogue of pivotal transcripts involved in sexual development and determination (206 transcripts) as well as in biosynthesis and storage of lipids (119 transcripts) in male and female specimens. This study provides a valuable transcriptomic resource and will contribute for the future conservation of the species as well as the exploitation in aquaculture settings.HighlightsAssembly of a reference transcriptome of Paracentrotus lividus gonads.Differential gene expression between males and female gonads of Paracentrotus lividus.Identification and validation of pivotal genes involved in biosynthesis and storage of lipids.
Loss of Secretory Pathway Ca2+ ATPase (SPCA1) Impairs Insulin Secretion and Reduces Autophagy in the Pancreatic Islet
Authors: Bone Robert N. , Tong Xin , Weaver Staci A. , Muralidharan Charanya , Krishnan Preethi , Kono Tatsuyoshi , Evans-Molina Carmella 
Published: August 2021

AbstractThe β cell Golgi apparatus serves as a significant store of intracellular Ca2+ and an important site of proinsulin maturation. However, the contribution of Golgi Ca2+ to diabetes pathophysiology is unknown. The Golgi primarily utilizes the Secretory Pathway Ca2+ ATPase (SPCA1) to maintain intraluminal Ca2+ stores, and loss of SPCA1 has been linked to impaired Golgi function in other cell types. Here, we demonstrated that SPCA1 expression is decreased in islets from diabetic mice and human organ donors with type 2 diabetes, suggesting SPCA1 may impact diabetes development. INS-1 β cells lacking SPCA1 (SPCA1KO) showed reduced intraluminal Golgi Ca2+ levels, reduced glucose-stimulated insulin secretion (GSIS), and increased insulin content. Islets from SPCA1 haploinsufficient mice (SPCA1+/-) exhibited reduced GSIS, altered glucose-induced Ca2+ oscillations, and altered insulin granule maturation. Autophagy can regulate granule homeostasis, therefore we induced autophagy with Torin1 and found that SPCA1KO cells and SPCA1+/- islets had reduced levels of the autophagosome marker LC3-II. Furthermore, SPCA1KO LC3-II were unchanged after blocking autophagy initiation or autophagolysosome fusion and acidification. Thus, we concluded that β cell SPCA1 plays an important role in the maintenance of Golgi Ca2+ homeostasis and reduced Golgi Ca2+ impairs autophagy initiation and may impact insulin granule homeostasis.
Relationship between COVID-19 infection and neurodegeneration: Computational insight into interactions between the SARS-CoV-2 spike protein and the monoamine oxidase enzymes
Authors: Hok Lucija , Rimac Hrvoje , Mavri Janez , Vianello Robert 
Published: August 2021

ABSTRACTAlthough COVID-19 has been primarily associated with pneumonia, recent data show that its causative agent, the SARS-CoV-2 coronavirus, can infect many vital organs beyond the lungs, including the heart, kidneys and the brain. The literature agrees that COVID-19 is likely to have long-term mental health effects on infected individuals, which signifies a need to understand the role of the virus in the pathophysiology of brain disorders that is currently unknown and widely debated. Our docking and molecular dynamic simulations show that the affinity of the spike protein from the wild type (WT) and the South African B.1.351 (SA) variant towards the MAO enzymes is comparable to that for its ACE2 receptor. This allows for the WT/SA…MAO complex formation, which changes MAO affinities for their neurotransmitter substrates, thus consequently impacting the rates of their metabolic conversion and misbalancing their levels. Knowing that this fine regulation is strongly linked with the etiology of various brain pathologies, these results are the first to highlight the possibility that the interference with the brain MAO catalytic activity is responsible for the increased neurodegenerative illnesses following a COVID-19 infection, thus placing a neurobiological link between these two conditions in the spotlight. Since the obtained insight suggests that a more contagious SA variant causes even larger disturbances, and with new and more problematic strains likely emerging in the near future, we firmly advise that the presented prospect of the SARS-CoV-2 induced neurological complications should not be ignored, but rather requires further clinical investigations to achieve an early diagnosis and timely therapeutic interventions.TABLE OF CONTENTS ENTRYDocking and molecular dynamic simulations highlight the possibility that the interference with the brain monoamine oxidase (MAO) catalytic activity is responsible for the increased neurodegenerative illnesses following a COVID-19 infection.
Songbird subthalamic neurons signal song timing and error and project to dopaminergic midbrain
Authors: Das Anindita , Goldberg Jesse H. 
Published: August 2021

AbstractSkill learning requires motor output to be evaluated against internal performance benchmarks. In songbirds, ventral tegmental area (VTA) dopamine neurons (DA) signal performance errors important for learning, but it remains unclear which brain regions project VTA and how these inputs may implement the sensorimotor comparisons necessary for error computation. Here we find that the songbird subthalamic nucleus (STN) projects to VTA and that STN microstimulation can excite VTA neurons. We also discover that STN receives inputs from auditory cortical and ventral pallidal brain regions previously implicated in song evaluation. In the first neural recordings from songbird STN, we discover that the activity of most STN neurons is associated with body movements and not singing, but a small fraction of neurons exhibits precise song timing and performance error signals consistent with performance evaluation. Together our results implicate the STN-VTA projection as an evolutionarily conserved pathway important for motor learning and expand the territories of songbird brain associated with song learning.New & NoteworthySongbird subthalamic (STN) neurons exhibit song-timing and performance error signals and are interconnected with auditory pallium, ventral pallidum and ventral tegmental area, three areas important for song learning.