bluuebunny/crossref_metadata_2025_split huggingface dataset:
DWV infection and replication at the early stagein vitrousing honey bee pupal cells
Authors: Wu Yunfei , Li Jing , Kadowaki Tatsuhiko 
Published: September 2020

AbstractDeformed wing virus (DWV) has been best characterized among honey bee viruses; however, very little is known about the mechanisms of viral infection and replication due to the lack of honey bee cell lines. To resolve this problem, we establishedin vitrosystem to reconstitute DWV binding and entry to the host cell followed by translation of the genome RNA and the polyprotein processing with honey bee pupal cells. Using this system, P-domain of VP1 was found to be essential for DWV infection/replication but not binding/entry to the cell. DWV efficiently infects/replicates in cells derived from early but not late pupa, suggesting that the undifferentiated cells are targeted for the viral infection/replication. Furthermore, we found that inhibitors for mammalian picornavirus 3C-Protease, Rupintrivir and Quercetin suppress DWV infection/replication, indicating that thisin vitrosystem is also useful for screening a compound to modify the viral infection/replication. Ourin vitrosystem should help to understand the mechanisms of DWV infection and replication at the early stage.ImportanceRecent decline of managed honey bee colonies has been driven by the pathogens and parasites. However, studying the mechanisms of pathogen infection and replication in honey bee at molecular and cellular levels has been challenging. DWV is the most prevalent virus in honey bee across the globe and we establishedin vitrosystem to reconstitute the viral infection and replication with the primary pupal cells. Using RNA-dependent RNA polymerase (RdRP) and the negative strand of DWV genome RNA as markers, we show that the pupal cells can support DWV infection and at least replication at the early stage. The results shown in this report indicate that ourin vitrosystem helps to uncover the mechanisms of DWV infection and replication. Furthermore, it is also feasible to conduct a large scale screening for compounds to inhibit or stimulate DWV infection/replication.
Sex dimorphism in European sea bass (Dicentrarchus labraxL.): new insights into sex-related growth patterns during very early life stages
Authors: Faggion Sara , Vandeputte Marc , Vergnet Alain , Clota Frédéric , Blanc Marie-Odile , Sanchez Pierre , Ruelle François , Allal François 
Published: September 2020

AbstractThe European sea bass (Dicentrarchus labrax) exhibits female-biased sexual size dimorphism (SDD) early in development. New tagging techniques provide the opportunity to monitor individual sex-related growth during the post-larval and juvenile stages.We produced an experimental population through artificial fertilization and followed a rearing-temperature protocol (∼16 °C from hatching to 112 days post-hatching, dph; ∼20 °C from 117 to 358 dph) targeting a roughly balanced sex ratio. The fish were tagged with microchips between 61 and 96 dph in five tagging trials of 50 fish each; individual standard length (SL) was recorded through repeated biometric measurements performed between 83 to 110 dph via image analyses. Body weight (BW) was modelled using the traits measured on the digital pictures (i.e. SL, area, height, perimeter and volume). At 117 dph, the fish were tagged with microtags and regularly measured for SL and BW until 335 dph. The experiment ended at 358 dph with the sexing of the fish.The sex-ratio at the end of the experiment was significantly in favor of the females (65.9% vs. 34.1%). The females were significantly longer and heavier than the males from 103 dph (∼30 mm SL, ∼0.44 g BW) to 165 dph. A significant difference in the daily growth coefficient (DGC) was observed only between 96 and 103 dph, suggesting a physiological or biological change occurring during this period.The female-biased SSD pattern in European sea bass is thus strongly influenced by very early growth differences between sexes, in any case long before gonadal sex differentiation has been started. This leads to the hypothesis that early growth may be a cause rather than a consequence of sex determination in sea bass.
Reduced Successor Representation Potentially Interferes with Cessation of Habitual Reward-Seeking
Authors: Shimomura Kanji , Kato Ayaka , Morita Kenji 
Published: September 2020

AbstractDifficulty in cessation of drinking, smoking, or gambling has been widely recognized. Conventional theories proposed relative dominance of habitual over goal-directed control, but human studies have not convincingly supported them. Referring to the recently suggested “successor representation” of states that enables partially goal-directed control, we propose a dopamine-related mechanism potentially underlying the difficulty in resisting habitual reward-seeking, common to substance and non-substance reward. Consider that a person has long been taking a series of actions leading to a certain reward without resisting temptation. Given the suggestions of the successor representation and the dimension reduction in the brain, we assumed that the person has acquired a dimension-reduced successor representation of states based on the goal state under the established non-resistant policy. Then, we show that if the person changes the policy to resist temptation, a large positive reward prediction error (RPE) becomes generated upon eventually reaching the goal, and it sustains given that the acquired state representation is so rigid that it does not change. Inspired by the anatomically suggested spiral striatum-midbrain circuit and the theoretically proposed spiraling accumulation of RPE bias in addiction, we further simulated the influence of RPEs generated in the goal-based representation system on another system representing individual actions. We then found that such an influence could potentially enhance the propensity of non-resistant choice. These results suggest that the inaccurate value estimation in the reduced successor representation system and its influence through the spiral striatum-midbrain circuit might contribute to the difficulty in cessation of habitual reward-seeking.
Comprehensive genomic analysis reveals virulence factors and antibiotic resistance genes inPantoea agglomeransKM1, a potential opportunistic pathogen
Authors: Guevarra Robin B. , Magez Stefan , Peeters Eveline , Chung Mi Sook , Kim Kyung Hyun , Radwanska Magdalena 
Published: September 2020

AbstractPantoea agglomeransis a Gram-negative aerobic bacillus causing a wide range of opportunistic infections in humans including septicemia, pneumonia, septic arthritis, wound infections and meningitis. To date, the determinants of virulence, antibiotic resistance, metabolic features conferring survival and host-associated pathogenic potential of this bacterium remain largely underexplored. In this study, we sequenced and assembled the whole-genome ofP. agglomeransKM1 isolated from kimchi in South Korea. The genome contained one circular chromosome of 4,039,945 bp, 3 mega plasmids, and 2 prophages. The phage-derived genes encoded integrase, lysozyme and terminase. Six CRISPR loci were identified within the bacterial chromosome. Further in-depth analysis showed that the genome contained 13 antibiotic resistance genes conferring resistance to clinically important antibiotics such as penicillin G, bacitracin, rifampicin, vancomycin, and fosfomycin. Genes involved in adaptations to environmental stress were also identified which included factors providing resistance to osmotic lysis, oxidative stress, as well as heat and cold shock. The genomic analysis of virulence factors led to identification of a type VI secretion system, hemolysin, filamentous hemagglutinin, and genes involved in iron uptake and sequestration. Finally, the data provided here show that, the KM1 isolate exerted strong immunostimulatory properties on RAW 264.7 macrophagesin vitro. Stimulated cells produced Nitric Oxide (NO) and pro-inflammatory cytokines TNF-α, IL-6 and the anti-inflammatory cytokine IL-10. The upstream signaling for production of TNF-α, IL-6, IL-10, and NO depended on TLR4 and TLR1/2. While production of TNF-α, IL-6 and NO involved solely activation of the NF-κB, IL-10 secretion was largely dependent on NF-κB and to a lesser extent on MAPK Kinases. Taken together, the analysis of the whole-genome and immunostimulatory properties provided in-depth characterization of theP. agglomeransKM1 isolate shedding a new light on determinants of virulence that drive its interactions with the environment, other microorganisms and eukaryotic hosts.
Structural Coordinates: A novel approach to predict protein backbone conformation
Authors: Milchevskaya Vladislava , Nikitin Alexei M. , Lukshin Sergey A. , Filatov Ivan V. , Kravatsky Yuri V. , Tumanyan Vladimir G. , Esipova Natalia G. , Milchevskiy Yury V. 
Published: September 2020

AbstractMotivationLocal protein structure is usually described via classifying each peptide to a unique element from a set of pre-defined structures. These so-called structural alphabets may differ in the number of structures or the length of peptides. Most methods that predict the local structure of a protein from its sequence rely on this kind of classification. However, since all peptides assigned to the same class are indistinguishable, such an approach may not be sufficient to model protein folding with high accuracy.ResultsWe developed a method that predicts the structural representation of a peptide from its sequence. For 5-mer peptides, we achieved the Q16 classification accuracy of 67.9%, which is higher than what is currently reported in the literature. Importantly, our prediction method does not utilize information about protein homologues but only physicochemical properties of the amino acids and the statistics of the structures, but relies on a comprehensive feature-generation procedure based only on the protein sequence and the statistics of resolved structures. We also show that the 3D coordinates of a peptide can be uniquely recovered from its structural coordinates, and show the required conditions for that under various geometric constraints.AvailabilityThe online implementation of the method is provided freely athttp://pbpred.eimb.ruContactmilch@eimb.ruorvmilchev@uni-koeln.deSupplementary informationSupplementary data are available online athttp://pbpred.eimb.ru/S/index.html
MOVICS: an R package for multi-omics integration and visualization in cancer subtyping
Authors: Lu Xiaofan , Meng Jialin , Zhou Yujie , Jiang Liyun , Yan Fangrong 
Published: September 2020

AbstractSummaryStratification of cancer patients into distinct molecular subgroups based on multi-omics data is an important issue in the context of precision medicine. Here we presentMOVICS, an R package for multi-omics integration and visualization in cancer subtyping.MOVICSprovides a unified interface for 10 state-of-the-art multi-omics integrative clustering algorithms, and incorporates the most commonly used downstream analyses in cancer subtyping researches, including characterization and comparison of identified subtypes from multiple perspectives, and verification of subtypes in external cohort using a model-free approach for multiclass prediction.MOVICSalso creates feature rich customizable visualizations with minimal effort.Availability and implementationMOVICSpackage and online tutorial are freely available athttps://github.com/xlucpu/MOVICS.
Individualized cyclic mechanical loading improves callus properties during the remodelling phase of fracture healing in mice as assessed from time-lapsed in vivo imaging
Authors: Wehrle Esther , Paul Graeme R , Tourolle né Betts Duncan C , Kuhn Gisela A , Müller Ralph 
Published: September 2020

AbstractFracture healing is regulated by mechanical loading. Understanding the underlying mechanisms during the different healing phases is required for targeted mechanical intervention therapies. Here, the influence of individualized cyclic mechanical loading on the remodelling phase of fracture healing was assessed in a mouse femur defect model. After bridging of the defect, a loading group (n=10) received individualized cyclic mechanical loading (8-16 N, 10 Hz, 5 min, 3x/week) based on computed strain distribution in the callus using animal-specific real-time micro-finite element analysis. Controls (n=10) received 0 N treatment at the same post-operative time-points. By registration of consecutive scans, structural and dynamic callus morphometric parameters were followed in three callus sub-volumes and the adjacent cortex showing that the remodelling phase of fracture healing is highly responsive to cyclic mechanical loading with changes in dynamic parameters leading to significantly larger callus formation and mineralization. Loading-mediated maintenance of callus remodelling was associated with distinct effects on Wnt-signalling-associated molecular targets Sclerostin and RANKL in callus sub-regions and the adjacent cortex. Given these distinct local protein expression patterns induced by cyclic mechanical loading, the femur defect loading model with individualized load application seems suitable to understand the local spatio-temporal mechano-molecular regulation of the different fracture healing phases.
Single-molecule measurements reveal that PARP1 condenses DNA by loop formation
Authors: Bell Nicholas A. W. , Haynes Philip J. , Brunner Katharina , Maia de Oliveira Taiana , Flocco Maria , Hoogenboom Bart W. , Molloy Justin E. 
Published: September 2020

ABSTRACTPoly(ADP-ribose) polymerase 1 (PARP1) is an abundant nuclear enzyme that plays important roles in DNA repair, chromatin organization and transcription regulation. Although binding and activation of PARP1 by DNA damage sites has been extensively studied, little is known about how PARP1 binds to long stretches of undamaged DNA and how it could shape chromatin architecture. Here, using a combination of single-molecule techniques including magnetic tweezers and atomic force microscopy, we show that PARP1 binds and condenses undamaged, kilobase-length DNA subject to sub-picoNewton mechanical forces. Decondensation by high force proceeds through a series of discrete increases in extension, indicating that PARP1 stabilizes loops of DNA. This model is supported by DNA braiding experiments which show that PARP1 can bind at the intersection of two separate DNA molecules. PARP inhibitors do not affect the level of condensation of undamaged DNA, but act to block condensation reversal for damaged DNA in the presence of NAD+. Our findings establish a mechanism for PARP1 in the organization of chromatin structure.
Convergent adaptation in mitochondria of phylogenetically distant birds: does it exist?
Authors: Burskaia Valentina , Artyushin Ilja , Potapova Nadezhda , Konovalov Kirill , Bazykin Georgii A. 
Published: September 2020

AbstractIn a wide range of taxa, proteins encoded by mitochondrial genomes are involved in adaptation to lifestyle that requires oxygen starvation or elevation of metabolism rate. It remains poorly understood to what extent adaptation to similar conditions is associated with parallel changes in these proteins. We search for genetic signal of parallel or convergent evolution in recurrent molecular adaptation to high altitude, migration, diving, wintering, unusual flight abilities, or loss of flight in mitochondrial genomes of birds. Developing on previous work, we design an approach for detection of recurrent coincident changes in genotype and phenotype, indicative of an association between the two. We describe a number of candidate sites involved in recurrent adaptation inNDgenes. However, we find that the majority of convergence events can be explained by random coincidences without invoking adaptation.
Stable transplantation of human mitochondrial DNA by high-throughput, pressurized mitochondrial delivery
Authors: Sercel Alexander J. , Patananan Alexander N. , Man Tianxing , Wu Ting-Hsiang , Yu Amy K. , Guyot Garret W. , Rabizadeh Shahrooz , Niazi Kayvan R. , Chiou Pei-Yu , Teitell Michael A. 
Published: September 2020

ABSTRACTGenerating mammalian cells with specific mtDNA-nDNA combinations is desirable but difficult to achieve and would be enabling for studies of mitochondria-nucleus communication and coordination in controlling cell fates and functions. We developed ‘MitoPunch’, a force-actuated mitochondrial transfer device, to deliver isolated mitochondria into numerous target mammalian cells simultaneously. MitoPunch and MitoCeption, an alternative force-based mitochondrial transfer approach, both yield stable isolated mitochondrial recipient (SIMR) cells that permanently retain exogenous mtDNA, whereas coincubation of mitochondria with cells does not yield SIMR cells. Although a typical MitoPunch or MitoCeption delivery results in dozens of immortalized SIMR clones with restored oxidative phosphorylation, only MitoPunch can produce replication-limited, non-immortal human SIMR clones. The MitoPunch device is versatile, inexpensive to assemble, and easy to use for engineering mtDNA-nDNA combinations to enable fundamental studies and potential translational applications.
Lung lineage transcription factor NKX2-1 epigenetically resolves opposing cell fates in vivo
Authors: Little Danielle R. , Lynch Anne M. , Yan Yun , Akiyama Haruhiko , Kimura Shioko , Chen Jichao 
Published: September 2020

ABSTRACTDifferential use of identical DNA sequences leads to distinct tissue lineages and then multiple cell types within a lineage, an epigenetic process central to progenitor and stem cell biology. The associated genomic changes, especially in native tissues, remain insufficiently understood, and are hereby addressed in the mouse lung, where the same lineage transcription factor NKX2-1 promotes the diametrically opposed alveolar type 1 (AT1) and AT2 cell fates. We show that the cell-type-specific function of NKX2-1 is attributed to its differential chromatin binding that is acquired or retained during development in coordination with partner transcriptional factors. Loss of YAP/TAZ redirects NKX2-1 from its AT1-specific to AT2-specific binding sites, leading to transcriptionally exaggerated AT2 cells when deleted in progenitors or AT1-to-AT2 conversion when deleted after fate commitment.Nkx2-1mutant AT1 and AT2 cells gain distinct accessible sites including those of the opposite fate while adopting the gastrointestinal fate, suggesting an epigenetic plasticity larger than a transcriptional one. Our genomic analysis of single or purified cells, coupled with precision genetics, provides an epigenetic roadmap of alveolar cell fate and potential, and introduces an experimental benchmark for unraveling the in vivo function of lineage transcription factors.
Attention network modulation via tRNS correlates with attention gain
Authors: Contò F. , Edwards G. , Tyler S. , Parrott D. , Grossman E.D. , Battelli L. 
Published: September 2020

AbstractTranscranial Random Noise Stimulation (tRNS) can enhance vision in the healthy and diseased brain. Yet, the impact of tRNS on large-scale cortical networks is still unknown. We investigated the impact of tRNS coupled with behavioral training on resting-state functional connectivity and attention. We trained human subjects for four consecutive days on two attention tasks, while receiving tRNS over the intraparietal sulci, the middle temporal areas, or sham stimulation. We measured resting state functional connectivity of nodes of the dorsal and ventral attention network (DVAN) before and after training. We found a strong behavioral improvement and increased connectivity within the DVAN after parietal stimulation only. Crucially, behavioral improvement positively correlated with connectivity measures. We conclude changes in connectivity is a marker for the enduring effect of tRNS upon behavior. Our results suggest that tRNS has strong potential to augment cognitive capacity in healthy individuals and promote recovery in the neurological population.
Predicting MEG brain functional connectivity using microstructural information
Authors: Messaritaki Eirini , Foley Sonya , Schiavi Simona , Magazzini Lorenzo , Routley Bethany , Jones Derek K. , Singh Krish D. 
Published: September 2020

AbstractUnderstanding how human brain microstructure influences functional connectivity is an important endeavor. In this work, magnetic resonance imaging data from ninety healthy participants were used to calculate structural connectivity matrices using the streamline count, fractional anisotropy, radial diffusivity and a myelin measure (derived from multicomponent relaxometry) to assign connection strength. Unweighted binarized structural connectivity matrices were also constructed. Magnetoencephalography resting-state data from those participants were used to calculate functional connectivity matrices, via correlations of the Hilbert envelopes of beamformer timeseries at the delta, theta, alpha and beta frequency bands. Non-negative matrix factorization was performed to identify the components of the functional connectivity. Shortest-path-length and search-information analyses of the structural connectomes were used to predict functional connectivity patterns for each participant.The microstructure-informed algorithms predicted the components of the functional connectivity more accurately than they predicted the total functional connectivity. This provides a methodology for better understanding of functional mechanisms. The shortest-path-length algorithm exhibited the highest prediction accuracy. Of the weights of the structural connectivity matrices, the streamline count and the myelin measure gave the most accurate predictions, while the fractional anisotropy performed poorly. Overall, different structural metrics paint very different pictures of the structural connectome and its relationship to functional connectivity.
Neural selectivity for visual motion in macaque area V3A
Authors: Nakhla Nardin , Korkian Yavar , Krause Matthew R. , Pack Christopher C. 
Published: September 2020

AbstractThe processing of visual motion is carried out by dedicated pathways in the primate brain. These pathways originate with populations of direction-selective neurons in the primary visual cortex, which project to dorsal structures like the middle temporal (MT) and medial superior temporal (MST) areas. Anatomical and imaging studies have suggested that area V3A might also be specialized for motion processing, but there have been very few studies of single-neuron direction selectivity in this area. We have therefore performed electrophysiological recordings from V3A neurons in two macaque monkeys (one male and one female) and measured responses to a large battery of motion stimuli that includes translation motion, as well as more complex optic flow patterns. For comparison, we simultaneously recorded the responses of MT neurons to the same stimuli. Surprisingly, we find that overall levels of direction selectivity are similar in V3A and MT and moreover that the population of V3A neurons exhibits somewhat greater selectivity for optic flow patterns. These results suggest that V3A should be considered as part of the motion processing machinery of the visual cortex, in both human and non-human primates.Significance statementAlthough area V3A is frequently the target of anatomy and imaging studies, little is known about its functional role in processing visual stimuli. Its contribution to motion processing has been particularly unclear, with different studies yielding different conclusions. We report a detailed study of direction selectivity in V3A. Our results show that single V3A neurons are, on average, as capable of representing motion direction as are neurons in well-known structures like MT. Moreover, we identify a possible specialization for V3A neurons in representing complex optic flow, which has previously been thought to emerge in higher-order brain regions. Thus it appears that V3A is well-suited to a functional role in motion processing.