bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of natural scene representation in primary visual cortex requires early postnatal experience
Authors: Kowalewski Nina , Kauttonen Janne , Stan Patricia L. , Jeon Brian B. , Fuchs Thomas , Chase Steven M. , Lee Tai Sing , Kuhlman Sandra J. 
Published: October 2020

SummaryThe development of the visual system is known to be shaped by early-life experience. To identify response properties that contribute to enhanced natural scene representation, we performed calcium imaging of excitatory neurons in the primary visual cortex (V1) of awake mice raised in three different conditions (standard-reared, dark-reared, and delayed-visual experience) and compared neuronal responses to natural scene features relative to simpler grating stimuli that varied in orientation and spatial frequency. We assessed population selectivity in V1 using decoding methods and found that natural scene discriminability increased by 75% between the ages of 4 to 6 weeks. Both natural scene and grating discriminability were higher in standard-reared animals compared to those raised in the dark. This increase in discriminability was accompanied by a reduction in the number of neurons that responded to low-spatial frequency gratings. At the same time there was an increase in neuronal preference for natural scenes. Light exposure restricted to a 2-4 week window during adulthood did not induce improvements in natural scene nor in grating stimulus discriminability. Our results demonstrate that experience reduces the number of neurons required to effectively encode grating stimuli and that early visual experience enhances natural scene discriminability by directly increasing responsiveness to natural scene features.
Aird: A computation-oriented mass spectrometry data format enables higher compression ratio and less decoding time
Authors: Lu Miaoshan , An Shaowei , Wang Ruimin , Wang Jinyin , Yu Changbin 
Published: October 2020

ABSTRACTWith the precision of mass spectrometer going higher and the emergence of data independence acquisition (DIA), the file size is increasing rapidly. Beyond the widely-used open format mzML (Deutsch 2008), near-lossless or lossless compression algorithms and formats have emerged. The data precision is often related to the instrument and subsequent processing algorithms. Unlike storage-oriented formats, which focusing more on lossless compression and compression rate, computation-oriented formats focus as much on decoding speed and disk read strategy as compression rate. Here we describe “Aird", an opensource and computation-oriented format with controllable precision, flexible indexing strategies and high compression rate. Aird uses JavaScript Object Notation (JSON) for metadata storage, multiple indexing, and reordered storage strategies for higher speed of data randomly reading. Aird also provides a novel compressor called Zlib-Diff-PforDelta (ZDPD) for m/z data compression. Compared with Zlib only, m/z data size is about 65% lower in Aird, and merely takes 33% decoding time.AvailabilityAird SDK is written in Java, which allow scholars to access mass spectrometry data efficiently. It is available athttps://github.com/Propro-Studio/Aird-SDKAirdPro can convert vendor files into Aird files, which is available athttps://github.com/Propro-Studio/AirdPro
Information Decomposition in the Frequency Domain: a New Framework to Study Cardiovascular and Cardiorespiratory Oscillations
Authors: Faes Luca , Pernice Riccardo , Mijatovic Gorana , Antonacci Yuri , Krohova Jana Cernanova , Javorka Michal , Porta Alberto 
Published: October 2020

SummaryWhile cross-spectral and information-theoretic approaches are widely used for the multivariate analysis of physiological time series, their combined utilization is far less developed in the literature. This study introduces a framework for the spectral decomposition of multivariate information measures, which provides frequency-specific quantifications of the information shared between a target and two source time series and of its expansion into amounts related to how the sources contribute to the target dynamics with unique, redundant and synergistic information. The framework is illustrated in simulations of linearly interacting stochastic processes, showing how it allows to retrieve amounts of information shared by the processes within specific frequency bands which are otherwise not detectable by time-domain information measures, as well as coupling features which are not detectable by spectral measures. Then, it is applied to the time series of heart period, systolic and diastolic arterial pressure and respiration variability measured in healthy subjects monitored in the resting supine position and during head-up tilt. We show that the spectral measures of unique, redundant and synergistic information shared by these variability series, integrated within specific frequency bands of physiological interest, reflect the mechanisms of short term regulation of cardiovascular and cardiorespiratory oscillations and their alterations induced by the postural stress.
The rate of whole-genome duplication can be accelerated by hybridization
Authors: Marsit S. , Hénault M. , Charron G. , Fijarczyk A. , Landry C. R 
Published: October 2020

AbstractHybridization and polyploidization are powerful mechanisms of speciation. Hybrid speciation often coincides with whole-genome duplication (WGD) in eukaryotes. This suggests that WGD allows hybrids to thrive by restoring fertility and/or increasing access to adaptive mutations. Alternatively, it has been suggested that hybridization itself may trigger WGD. Testing these models requires quantifying the rate of WGD in hybrids without the confounding effect of natural selection. By measuring the spontaneous rate of WGD of 1304 yeast crosses evolved under relaxed selection, we show that some genotypes are more prone to WGD and WGD can be triggered by hybridization. We also find that higher WGD rate correlates with higher genomic instability and that WGD increases fertility and genetic variability. These results provide evidence that hybridization itself can promote WGD, which in turn facilitates the evolution of hybrids.
Transfer function for YAP/TAZ nuclear translocation revealed through spatial systems modeling
Authors: Scott Kiersten E. , Fraley Stephanie I. , Rangamani Padmini 
Published: October 2020

ABSTRACTYAP/TAZ is a master regulator of mechanotransduction whose functions rely on translocation from the cytoplasm to the nucleus in response to diverse physical cues. Substrate stiffness, substrate dimensionality, and cell shape are all input signals for YAP/TAZ, and through this pathway, regulate critical cellular functions and tissue homeostasis. Yet, the relative contributions of each biophysical signal and the mechanisms by which they synergistically regulate YAP/TAZ in realistic tissue microenvironments that provide multiplexed input signals remains unclear. For example, in simple 2D culture, YAP/TAZ nuclear localization correlates strongly with substrate stiffness, while in 3D environments, YAP/TAZ translocation can increase with stiffness, decrease with stiffness, or remain unchanged. Here, we develop a spatial model of YAP/TAZ translocation to enable quantitative analysis of the relationships between substrate stiffness, substrate dimensionality, and cell shape. Our model couples cytosolic stiffness to nuclear mechanics to replicate existing experimental trends, and extends beyond current data to predict that increasing substrate activation area through changes in culture dimensionality, while conserving cell volume, forces distinct shape changes that result in nonlinear effect on YAP/TAZ nuclear localization. Moreover, differences in substrate activation area versus total membrane area can account for counterintuitive trends in YAP/TAZ nuclear localization in 3D culture. Based on this multiscale investigation of the different system features of YAP/TAZ nuclear translocation, we predict that how a cell reads its environment is a complex information transfer function of multiple mechanical and biochemical factors. These predictions reveal design principles of cellular and tissue engineering for YAP/TAZ mechanotransduction.STATEMENT OF SIGNIFICANCEIn chemical engineering, a transfer function is a mathematical function that models the output of a reactor for all possible inputs, and enables the reliable design and operation of complex reaction systems. Here, we apply this principle to cells to derive the transfer function by which substrate stiffness is converted into YAP/TAZ nuclear localization. This function is defined by a spatial model of the YAP/TAZ mechano-chemical sensing network, wherein key spatial and physical inputs to the system, namely cell and nuclear shape, surface area to volume ratios of cytoplasmic and nuclear compartments, substrate dimensionality, substrate activation area, and substrate stiffness, are all integrated. The resulting model accounts for seemingly contradictory experimental trends and lends new insight into controlling YAP/TAZ signalling.
The Adaptor Protein Complex 1 limits E-cadherin endocytosis during epithelial morphogenesis
Authors: Moreno Miguel Ramírez , Boswell Katy , Bulgakova Natalia A. 
Published: October 2020

AbstractIntracellular trafficking regulates the distribution of transmembrane proteins including the key determinants of epithelial polarity and adhesion. The Adaptor Protein 1 (AP-1) complex is the key regulator of vesicle sorting, which binds a large number of specific cargos. We examined roles of the AP-1 complex in epithelial morphogenesis, using theDrosophilawing as a paradigm. We found that AP-1 knockdown leads to ectopic folds caused by trafficking defects of integrins. This occurs concurrently with an increase in the apical cell area and induction of cell death due to defects in E-cadherin trafficking. We discovered a distinct pool of AP-1 localizes at the apical Adherens Junctions, where it limits internalization of E-cadherin from the cell surface. Upon AP-1 knockdown, the accompanying hyperinternalization of E-cadherin induces cell death by an uncharacterised mechanism with a potential tumour-suppressive role. Simultaneously, cells increase expression of E-cadherin in a compensatory mechanism to maintain cell-cell adhesion.
Performances of NeuMoDx, a random-access system for HBV-DNA and HCV-RNA quantification
Authors: Besombes Juliette , Pronier Charlotte , Lefevre Charles , Lagathu Gisèle , Maillard Anne , Grolhier Claire , Thibault Vincent 
Published: October 2020

AbstractViral loads (VL) monitoring for hepatitis B and C is essential to evaluate disease progression and treatment response. Automated, random-access rapid systems are becoming standard to provide reliable VL to clinicians. The aim of this study was to evaluate the analytical performances of the recently launched NeuMoDx™for HBV-DNA and HCV-RNA quantification. Clinical samples routinely quantified on the Beckman-Veris system were either retrospectively (frozen samples; HBV n=178, HCV n=249), or in parallel (fresh primary tubes; HBV n=103, HCV n=124) tested using NeuMoDx™. Linearity range was assessed on serial dilutions of high tittered plasmas containing different genotypes for HBV (A-E, n=10) and HCV (1a-b, 2-5, n=12). Overall test failure, mostly internal control amplification failure, was 2.3% and was not influenced by matrix types. For HBV-VL, Kappa agreement was 74%, with 27 (12.6%) discrepancies. Correlation between HBV assays on 72 quantified samples by both methods was excellent (r=0.963) with a mean bias (NeuMoDx™-Veris) of 0.21 log IU/mL. For HCV-VL, Kappa agreement reached 94%, with 9 (2.8%) discrepancies. The r-correlation factor between assays on 104 samples was 0.960 with a mean bias of −0.14 log IU/mL (NeuMoDx™-Veris). Serial dilutions confirmed the claimed linear ranges for all HBV and HCV genotypes. The mean turnaround time was 72’ [55-101] for HBV and 96’ [78-133] for HCV. These results obtained on the NeuMoDx™confirmed the overall good functionality of the system with a short turn-around-time, full traceability and easy handling. These results on HBV- and HCV-VL look promising and should be challenged with further comparisons.
Differentialin vitroactivity of individual drugs and bedaquiline-rifabutin combinations against actively multiplying and nutrient-starvedMycobacterium abscessus
Authors: Lee Jin , Ammerman Nicole , Agarwal Anusha , Naji Maram , Li Si-Yang , Nuermberger Eric 
Published: October 2020

AbstractCurrent treatment options for lung disease caused byMycobacterium abscessuscomplex infections have limited effectiveness. To maximize the use of existing antibacterials and to help inform regimen design for treatment, we assessed thein vitrobactericidal activity of single drugs against actively multiplying and net non-replicatingM. abscessuspopulations in nutrient-rich and nutrient starvation conditions, respectively. As single drugs, bedaquiline and rifabutin exerted bactericidal activity only against nutrient-starved and actively growingM. abscessus, respectively. However, when combined, both bedaquiline and rifabutin were able to specifically contribute bactericidal activity at relatively low, clinically relevant concentrations against both replicating and non-replicating bacterial populations. The addition of a third drug, amikacin, further enhanced the bactericidal activity of the bedaquiline-rifabutin combination against nutrient-starvedM. abscessus. Overall, thesein vitrodata suggest that bedaquiline-rifabutin may be a potent backbone combination to support novel treatment regimens forM. abscessusinfections. This rich dataset of differential time-and concentration-dependent activity of drugs, alone and together, againstM. abscessusalso highlights several issues affecting interpretation and translation ofin vitrofindings.
The impact of anorexia nervosa and BMI polygenic risk on childhood growth: a 20-year longitudinal population-based study
Authors: Abdulkadir Mohamed , Hübel Christopher , Herle Moritz , Loos Ruth J.F. , Breen Gerome , Bulik Cynthia M. , Micali Nadia 
Published: October 2020

BackgroundDeviating growth from the norm during childhood has been associated with anorexia nervosa (AN) and obesity later in life. In this study, we examined whether polygenic scores (PGSs) for AN and BMI are associated with growth trajectories spanning the first two decades of life.MethodsAN-PGS and BMI-PGS were calculated for participants of the Avon Longitudinal Study of Parents and Children (ALSPAC; N=8,654). Using generalized (mixed) linear models, we associated PGSs with trajectories of weight, height, body mass index (BMI), fat mass index (FMI), lean mass index (LMI), and bone mineral density (BMD).ResultsFemale participants with one SD higher AN-PGS had on average 0.004% slower growth in BMI between the ages 6.5-24 years and a 0.4% slower growth in BMD between the ages 10-24 years. Higher BMI-PGS was associated with faster growth for BMI, FMI, LMI, BMD, and weight trajectories in both sexes throughout childhood. Female participants with both a high AN-PGS and a low BMI-PGS showed slower growth compared to those with both a low AN-PGS and a low BMI-PGS.ConclusionAN-PGS and BMI-PGS have detectable sex-specific effects on growth trajectories. Female participants with high AN-PGS and low BMI-PGS likely constitute a high-risk group for AN as their growth was slower compared to their peers with high PGS on both traits. Further research is needed to better understand how the AN-PGS and the BMI-PGS co-influence growth during childhood and whether high BMI-PGSs can mitigate the effects of a high AN-PGS.
Distinctcis-acting elements govern purine-responsive regulation of theLeishmania donovaninucleoside transporters, LdNT1 and LdNT2
Authors: Licon M. Haley , Goodstein Francesca , Ortiz Diana , Landfear Scott M. , Yates Phillip A. 
Published: October 2020

AbstractPurine salvage from the host is an obligatory process for all protozoan parasites. InLeishmania donovani, this is accomplished by four membrane nucleoside and nucleobase transporters, or LdNTs. Previously, we demonstrated that purine starvation invokes a robust stress response inLeishmaniaand characterized the proteomic changes involved. However, becauseLeishmaniado not control the transcription of individual genes, the underlying mechanisms responsible for these changes were ill-defined. LdNT1 and LdNT2 are among the most rapidly and significantly upregulated genes in purine-starvedL. donovaniparasites. Thus, to better understand post-transcriptional mechanisms of purine-responsive gene expression, we have examined regulation of these genes in molecular detail. Here we report that LdNT1 and LdNT2 are controlled by distinctcis-acting elements. In the case of LdNT2, mRNA abundance and translational enhancement under purine stress depend on a 76 nt-long polypyrimidine tract encoded in theLdNT2mRNA 3’-UTR. Transcripts containing theLdNT2polypyrimidine tract were found to localize to discrete cytoplasmic foci in purine-replete cells, suggesting that theLdNT2message may be stored in RNA granules at steady-state. In the case of LdNT1, we found that purine-responsiveness is conferred by a 48 nt-long polypyrimidine tract and additional upstream element, termed UE1. Both features are independently required for regulation, with the polypyrimidine tract and UE1 controlling mRNA abundance and translation, respectively. Together, these results highlight a remarkable degree of complexity in the regulation of theLeishmaniapurine stress response and set the stage for future investigations to identify the larger network of RNA-protein and protein-protein interactions involved.
Cystic Fibrosis Acidic Microenvironment Determines Antibiotic Susceptibility and Biofilm Formation ofPseudomonas aeruginosa
Authors: Lin Qiao , Pilewski Joseph M. , Di Y. Peter 
Published: October 2020

AbstractPseudomonas aeruginosais the most prevalent bacterial species that contributes to cystic fibrosis (CF) respiratory failure. The impaired function of cystic fibrosis transmembrane conductance regulator leads to abnormal epithelial Cl−/ HCO3−transport and acidification of airway surface liquid. However, it remains unclear whyPseudomonas aeruginosapreferentially colonizes in the CF lungs. In this study, we carried out studies to investigate if lower pH helpsPseudomonas aeruginosaadapt and thrive in the CF-like acidic lung environment. Our results reveal thatPseudomonas aeruginosagenerally forms more biofilm and induces antibiotic resistance faster in acidic conditions and that this can be reversed by returning the acidic environment to physiologically neutral conditions.Pseudomonas aeruginosaappears to be highly adaptive to the CF-like acidic pH environment. By studying the effects of an acidic environment on bacterial response, we may provide a new therapeutic option in preventing chronicPseudomonas aeruginosainfection and colonization.
Cas9-mediated Genome Editing Reveals a Significant Contribution of Calcium Signaling Pathways to Anhydrobiosis in Pv11
Authors: Miyata Yugo , Fuse Hiroto , Tokumoto Shoko , Hiki Yusuke , Deviatiiarov Ruslan , Yoshida Yuki , Yamada Takahiro G. , Cornette Richard , Gusev Oleg , Shagimardanova Elena , Funahashi Akira , Kikawada Takahiro 
Published: October 2020

AbstractPv11 is an insect cell line established from the midgePolypedilum vanderplankithat exhibits an extreme desiccation tolerance known as anhydrobiosis. Pv11 has also an anhydrobiotic ability which is induced by trehalose treatment. Here we report the successful construction of the genome editing system for Pv11 cells and its application for identifying the signaling pathways in the anhydrobiosis. Using the Cas9-mediated gene knock-in system, we established GCaMP3-stably expressing Pv11 cells to monitor intracellular Ca2+mobilization. Intriguingly, trehalose treatment evoked a transient increase of cytosolic Ca2+concentration, and further experiments indicated the contribution of the calmodulin – calcineurin – NFAT pathway to the tolerance for trehalose treatment as well as the desiccation tolerance, while the calmodulin – calmodulin Kinase – CREB pathway conferred only the desiccation tolerance on Pv11 cells. Thus, our results show the critical contribution of the trehalose–induced Ca2+surge to the anhydrobiosis and the temporal different roles of each signaling pathway.
Quantitative Assays Reveal Cell Fusion at Minimal Levels of SARS-CoV-2 Spike Protein and Fusion-from-Without
Authors: Theuerkauf Samuel A. , Michels Alexander , Riechert Vanessa , Maier Thorsten J. , Flory Egbert , Cichutek Klaus , Buchholz Christian J. 
Published: October 2020

AbstractCell entry of the pandemic virus SARS-CoV-2 is mediated by its spike protein S. As main antigenic determinant, S protein is in focus of antibody-based prophylactic and therapeutic strategies. Besides particle-cell fusion, S mediates fusion between infected and uninfected cells resulting in syncytia formation. Here we present quantitative assay systems covering not only particle-cell and cell-cell fusion, but also demonstrating fusion-from-without (FFWO), the formation of syncytia induced by S-containing viral particles in absence of newly synthesized S protein. Based on complementation of split β-galactosidase and virus-like-particles (VLPs) displaying S protein, this assay can be performed at BSL-1. All three assays provided readouts with a high dynamic range and signal-to-noise ratios covering several orders of magnitude. The data obtained confirm the enhancing effect of trypsin and overexpression of angiotensin-converting enzyme 2 (ACE2) on membrane fusion. Neutralizing antibodies as well as sera from convalescent patients inhibited particle-cell fusion with high efficiency. Cell-cell fusion, in contrast, was only moderately inhibited despite requiring much lower levels of S protein, which were below the detection limit of flow cytometry and Western blot. The data indicate that syncytia formation as a pathological consequence in tissues of Covid-19 patients can proceed at low levels of S protein and may not be effectively prevented by antibodies.
Imperfect innate immune antagonism renders SARS-CoV-2 vulnerable towards IFN-γ and -λ
Authors: Hayn Manuel , Hirschenberger Maximilian , Koepke Lennart , Straub Jan H , Nchioua Rayhane , Christensen Maria H , Klute Susanne , Bozzo Caterina Prelli , Aftab Wasim , Zech Fabian , Conzelmann Carina , Müller Janis A , Badarinarayan Smitha Srinivasachar , Stürzel Christina M , Forne Ignasi , Stenger Steffen , Conzelmann Karl-Klaus , Münch Jan , Sauter Daniel , Schmidt Florian I , Imhof Axel , Kirchhoff Frank , Sparrer Konstantin MJ 
Published: October 2020

ABSTRACTThe innate immune system constitutes a powerful barrier against viral infections. However, it may fail because successful emerging pathogens, like SARS-CoV-2, evolved strategies to counteract it. Here, we systematically assessed the impact of 29 SARS-CoV-2 proteins on viral sensing, type I, II and III interferon (IFN) signaling, autophagy and inflammasome formation. Mechanistic analyses show that autophagy and type I IFN responses are effectively counteracted at different levels. For example, Nsp14 induces loss of the IFN receptor, whereas ORF3a disturbs autophagy at the Golgi/endosome interface. Comparative analyses revealed that antagonism of type I IFN and autophagy is largely conserved, except that SARS-CoV-1 Nsp15 is more potent in counteracting type I IFN than its SARS-CoV-2 ortholog. Altogether, however, SARS-CoV-2 counteracts type I IFN responses and autophagy much more efficiently than type II and III IFN signaling. Consequently, the virus is relatively resistant against exogenous IFN-α/β and autophagy modulation but remains highly vulnerable towards IFN-γ and -λ treatment. In combination, IFN-γ and -λ act synergistically, and drastically reduce SARS-CoV-2 replication at exceedingly low doses. Our results identify ineffective type I and II antagonism as weakness of SARS-CoV-2 that may allow to devise safe and effective anti-viral therapies based on targeted innate immune activation.