bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection
Authors: Youk Jeonghwan , Kim Taewoo , Evans Kelly V. , Jeong Young-Il , Hur Yongsuk , Hong Seon Pyo , Kim Je Hyoung , Yi Kijong , Kim Su Yeon , Na Kwon Joong , Bleazard Thomas , Kim Ho Min , Ivory Natasha , Mahbubani Krishnaa T. , Saeb-Parsy Kourosh , Kim Young Tae , Koh Gou Young , Choi Byeong-Sun , Ju Young Seok , Lee Joo-Hyeon 
Published: July 2020

AbstractSevere acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar cells (hACs). Characterising the pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hACs limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of long-term 3D hAT2 cultures as models for respiratory diseases.
Cognitive and Neural State Dynamics of Story Comprehension
Authors: Song Hayoung , Park Bo-yong , Park Hyunjin , Shim Won Mok 
Published: July 2020

AbstractUnderstanding a story involves a constant interplay of the accumulation of narratives and its integration into a coherent structure. This study characterizes cognitive state dynamics during story comprehension and the corresponding network-level reconfiguration of the whole brain. We presented movie clips of temporally scrambled sequences, eliciting fluctuations in subjective feelings of understanding. An understanding occurred when processing events with high causal relations to previous events. Functional neuroimaging results showed that, during moments of understanding, the brain entered into a functionally integrated state with increased activation in the default mode network (DMN). Large-scale neural state transitions were synchronized across individuals who comprehended the same stories, with increasing occurrences of the DMN-dominant state. The time-resolved functional connectivities predicted changing cognitive states, and the predictive model was generalizable when tested on new stories. Taken together, these results suggest that the brain adaptively reconfigures its interactive states as we construct narratives to causally coherent structures.
Shape-invariant perceptual encoding of dynamic facial expressions across species
Authors: Taubert N. , Stettler M. , Siebert R. , Spadacenta S. , Sting L. , Dicke P. , Thier P. , Giese Martin A. 
Published: July 2020

AbstractDynamic facial expressions are crucial for communication in primates. Due to the difficulty to control shape and dynamics of facial expressions across species, it is unknown how species-specific facial expressions are perceptually encoded and interact with the representation of facial shape. While popular neural-network theories predict a joint encoding of facial shape and dynamics, the neuromuscular control of faces evolved more slowly than facial shape, suggesting a separate encoding. To investigate this hypothesis, we developed photo-realistic human and monkey heads that were animated with motion-capture data from monkeys and human. Exact control of expression dynamics was accomplished by a Bayesian machine-learning technique. Consistent with our hypothesis, we found that human observers learned cross-species expressions very quickly, where face dynamics was represented independently of facial shape. This result supports the co-evolution of the visual processing and motor-control of facial expressions, while it challenges popular neural-network theories of dynamic expression-recognition.
A prion accelerates proliferation at the expense of lifespan
Authors: Garcia David M. , Campbell Edgar A. , Jakobson Christopher M. , Tsuchiya Mitsuhiro , DiNardo Acadia , Kaeberlein Matt , Jarosz Daniel F. 
Published: July 2020

ABSTRACTOrganisms often commit to one of two strategies: living fast and dying young or living slow and dying old. In fluctuating environments, however, switching between these two strategies could be advantageous. Lifespan is often inversely correlated with cell size and proliferation, which are both limited by protein synthesis. Here we report that a highly conserved RNA-modifying enzyme, the pseudouridine synthase Pus4/TruB, can act as a prion, endowing yeast with greater proliferation rates at the cost of a shortened lifespan. Cells harboring the prion can grow larger and exhibit altered protein synthesis. This epigenetic state, [BIG+] (better ingrowth), allows cells to heritably yet reversibly alter their translational program, leading to the differential expression of hundreds of proteins, including many that regulate proliferation and aging. Our data reveal a functional role for aggregation of RNA-modifying enzymes in driving heritable epigenetic states that transform cell growth and survival.
Regulation of GluA1 Phosphorylation by D-amphetamine and Methylphenidate in the Cerebellum
Authors: Cutando Laura , Puighermanal Emma , Castell Laia , Tarot Pauline , Bertaso Federica , Bonnavion Patricia , de Kerchove d’Exaerde Alban , Isingrini Elsa , Galante Micaela , Dallerac Glenn , Pascoli Vincent , Luscher Christian , Giros Bruno , Valjent Emmanuel 
Published: July 2020

AbstractPrescription stimulants, such as d-amphetamine or methylphenidate, are potent dopamine (DA) and norepinephrine (NE) releasers used to treat children and adults diagnosed for attention-deficit/hyperactivity disorder (ADHD). Although increased phosphorylation of the AMPA receptor subunit GluA1 at Ser845 (pS845-GluA1) in the striatum has been identified as an important cellular effector for the actions of these drugs, regulation of this posttranslational modification in the cerebellum has never been recognized. Here, we demonstrate that d-amphetamine and methylphenidate increase pS845-GluA1 in the membrane fraction in both vermis and lateral hemispheres of the mouse cerebellum. This regulation occurs selectively in Bergmann Glia Cells and requires intact norepinephrine release since the effects were abolished in mice lacking the vesicular monoamine transporter-2 selectively in NE neurons. Moreover, d-amphetamine-induced pS845-GluA1 was prevented by β1-adenoreceptor antagonist, whereas the blockade of dopamine D1 receptor had no effect. Additionally, we identified transcriptional alterations of several regulators of the cAMP/PKA pathway, which might account for the absence of pS845-GluA1 desensitization in mice repeatedly exposed to d-amphetamine or methylphenidate. Together, these results point to norepinephrine transmission as a key regulator of GluA1 phosphorylation in Bergmann Glial Cells, which may represent a new target for the treatment of ADHD.
Age-dependent ribosomal DNA variations and their effect on cellular function in mammalian cells
Authors: Watada Eriko , Li Sihan , Hori Yutaro , Fujiki Katsunori , Shirahige Katsuhiko , Inada Toshifumi , Kobayashi Takehiko 
Published: July 2020

AbstractThe ribosomal RNA gene, which consists of tandem repetitive arrays (rDNA repeat), is one of the most unstable regions in the genome. The rDNA repeat in the budding yeast is known to become unstable as the cell ages. However, it is unclear how the rDNA repeat changes in ageing mammalian cells. Using quantitative analyses, we identified age-dependent alterations in rDNA copy number and levels of methylation in mice. The degree of methylation and copy number of rDNA from bone marrow cells of 2-year-old mice were increased by comparison to 4-week-old mice in two mouse strains, BALB/cA and C57BL/6. Moreover, the level of pre-rRNA transcripts was reduced in older BALB/cA mice. We also identified many sequence variations among the repeats with two mutations being unique to old mice. These sequences were conserved in budding yeast and equivalent mutations shortened the yeast chronological lifespan. Our findings suggest that rDNA is also fragile in mammalian cells and alterations within this region have a profound effect on cellular function.Author SummaryThe ribosomal RNA gene (rDNA) is one of the most unstable regions in the genome due to its tandem repetitive structure. rDNA copy number in the budding yeast increases and becomes unstable as the cell ages. It is speculated that the rDNA produces an “aging signal” inducing senescence and death. However, it is unclear how the rDNA repeat changes during the aging process in mammalian cells. In this study, we attempted to identify the age-dependent alteration of rDNA in mice. Using quantitative single cell analysis, we show that rDNA copy number increases in old mice bone marrow cells. By contrast, the level of ribosomal RNA production was reduced because of increased levels of DNA methylation that represses transcription. We also identified many sequence variations in the rDNA. Among them, three mutations were unique to old mice and two of them were found in the conserved region in budding yeast. We then established a yeast strain with the old mouse-specific mutations and found this shortened the lifespan of the cells. These findings suggest that rDNA is also fragile in mammalian cells and alteration to this region of the genome affects cellular senescence.
Host adaptation and microbial competition driveRalstonia solanacearumphylotype I evolution in South Korea
Authors: Prokchorchik Maxim , Pandey Ankita , Moon Hayoung , Kim Wanhui , Jeon Hyelim , Poole Stephen , Segonzac Cécile , Sohn Kee Hoon , McCann Honour C. 
Published: July 2020

AbstractBacterial wilt caused by theRalstonia solanacearumspecies complex (RSSC) threatens the the cultivation of important crops worldwide. The exceptional diversity of type III secreted effector (T3E) families, high rates of recombination and broad host range of the RSSC hinder sustainable disease management strategies. We sequenced 30 phylotype I RSSC strains isolated from pepper (Capsicum annuum) and tomato (Solanum lycopersicum) in South Korea. These isolates span the diversity of phylotype I, have extensive effector repertoires and are subject to frequent recombination. Recombination hotspots among South Korean phylotype I isolates include multiple predicted contact-dependent inhibition loci, suggesting microbial competition plays a significant role inRalstoniaevolution. Rapid diversification of secreted effectors present challenges for the development of disease resistant plant varieties. We identified potential targets for disease resistance breeding by testing for allele-specific host recognition of T3Es present among South Korean phyloype I isolates. The integration of pathogen population genomics and molecular plant pathology contributes to the development of location-specific disease control and development of plant cultivars with durable resistance to relevant threats.RepositoriesAll genome sequences obtained in this study are deposited to NCBI GeneBank under BioProject number PRJNA593908
Investigating hospitalMycobacterium chelonaeinfection using whole genome sequencing and hybrid assembly
Authors: Gu Christopher H. , Zhao Chunyu , Hofstaedter Casey , Tebas Pablo , Glaser Laurel , Baldassano Robert , Bittinger Kyle , Mattei Lisa M. , Bushman Frederic D. 
Published: July 2020

AbstractMycobacterium chelonaeis a rapidly growing nontuberculous mycobacterium that is a common cause of nosocomial infections. Here we describe investigation of a possible nosocomial transmission ofM. chelonaeat the Hospital of the University of Pennsylvania (HUP).M. chelonaestrains with similar high-level antibiotic resistance patterns were isolated from two patients who developed post-operative infections at HUP in 2017, suggesting a possible point source infection. The isolates, along with other clinical isolates from other patients, were sequenced using the Illumina and Oxford Nanopore technologies. The resulting short and long reads were hybrid assembled into draft genomes. The genomes were compared by quantifying single nucleotide variants in the core genome and assessed using a control dataset for identity. We show that that allM. chelonaeisolates tested were highly divergent, consistent with environmental acquisition. Additionally, antibiotic resistance genes were predicted for our isolates, and several single nucleotide variants identified with the potential to modulated drug susceptibility, providing candidate resistance mechanisms.
Quality of life of people seeking for acupuncture treatment
Authors: Silva-Filho Reginaldo , Koike Marcia Kiyomi , da Silva Gizelda Monteiro 
Published: July 2020

AbstractBackgroundThe use of Acupuncture, part of Chinese Medicine, has grown as well as the need to understand its effects. The Quality of Life (QOL) assessment is an important way to have a global view of the patient.ObjectiveTo assess the QoL of people who seek acupuncture at the outpatient clinic of an acupuncture school.MethodsQOL assessment using WHOQOL-BREF applied only once to people who voluntarily sought for acupuncture at the general outpatient clinic of Faculdade EBRAMEC in 2016.ResultsPeople who sought for acupuncture treatment presented lower mean QoL value in all domains compared to normative values for Brazil, with physical domain presenting lower values than the other domains. It was also observed that male patients had higher values in the physical, psychological domains and general QOL compared to women.ConclusionOur data demonstrated that people seeking for acupuncture treatment presented lower values of QOL in comparison to a referential study with a Brazilian population, providing for the first time reference values measured by WHOQOL-bref, for patients seeking for acupuncture in the city of São Paulo.
The Amyloid Structure of Mouse RIPK3 (Receptor Interacting Protein Kinase 3) in Cell Necroptosis
Authors: Wu Xia-lian , Hu Hong , Dong Xing-qi , Zhang Jing , Wang Jian , Schwieters Charles D. , Liu Jing , Wu Guo-xiang , Li Bing , Lin Jing-yu , Wang Hua-yi , Lu Jun-xia 
Published: July 2020

ABSTRACTRIPK3 amyloid complex plays crucial roles in execution of TNF-induced necroptosis and in response to immune defense in both human and mouse. We have structurally characterized the mouse RIPK3 homogeneous self-assembly using solid-state NMR, illustrating a well-ordered N-shaped amyloid core structure featured with 3 parallel in-registerβ-sheets. The structure is different from previously published human RIPK1/RIPK3 hetero-amyloid complex. Functional studies indicate both RIPK1-RIPK3 binding and RIPK3 amyloid formation are essential but not sufficient for RIPK3-mediated necroptosis. The structural integrity of RIPK3 fibril with three β-strands is necessary for the signaling. Molecular dynamics simulation of the mouse RIPK1/RIPK3 model indicates less stable for the hetero-amyloid to adopt RIPK3 fibril conformation, suggesting a structural transformation of RIPK3 from RIPK1-RIPK3 binding to RIPK3 amyloid formation. This structural transformation is revealed for the first time, providing a missing link connecting RIPK1-RIPK3 binding to RIPK3 homo-oligomer formation in the signal transduction.
A formin-mediated cell wall- plasma membrane- cytoskeleton continuum is required for symbiotic infections inMedicago truncatula
Authors: Liang Pengbo , Schmitz Clara , Lace Beatrice , Ditengou Franck Anicet , Keller Jean , Libourel Cyril , Delaux Pierre-Marc , Ott Thomas 
Published: July 2020

ABSTRACTPlant cell infections are tightly orchestrated by cell wall (CW) alterations, plasma membrane (PM) resident signalling processes and dynamic remodelling of the cytoskeleton. During root nodule symbiosis these processes result in morpho-dynamic responses including root hair swelling and curling, PM invagination and polar growth of a tubular infection structure, the infection thread (IT). However, the molecular details driving and guiding these PM remodelling events remain to be unravelled. Here, we studied a formin protein (SYFO1) inM. truncatulathat is specifically induced during rhizobial infection. Phenotypical analysis ofsyfo1mutants clearly indicates that the encoded protein is required for efficient rhizobial colonization of root hairs. SYFO1 itself creates a proteinaceous bridge between the CW and the polarized cytoskeleton. It binds to CW components via a proline-rich N-terminal segment, which is indispensable for its function. On the cytoplasmic side of the PM SYFO1 is associated with actin accumulations supporting the hypothesis that it contributes to cell polarizationin vivo. This is further sustained by the fact that cell shape changes can be induced in a stimulus-dependent manner in root protoplasts expressing SYFO1. Taken together we provide evidence for the evolutionary re-wiring of a generic cytoskeleton modulator into a symbiosis-specific response.
Male and female reproductive fitness costs of an immune response in natural populations
Authors: De Lisle Stephen P. , Bolnick Daniel I. 
Published: July 2020

AbstractParasites can mediate host fitness both directly, via effects on survival and reproduction, or indirectly by inducing host immune defense with costly side-effects. The evolution of immune defense is determined by a complex interplay of costs and benefits of parasite infection and immune response, all of which may differ for male and female hosts in sexual lineages. Here, we examine fitness costs associated with an inducible immune defense in a fish-cestode host-parasite system. Cestode infection induces peritoneal fibrosis in threespine stickleback (Gasterosteus aculeatus), constraining cestode growth and sometimes encasing and killing the parasite. Surveying two wild populations of stickleback, we confirm that the presence of fibrosis scar tissue is associated with reduced parasite burden in both male and female fish. However, fibrotic fish had lower foraging success and reproductive fitness (reduced female egg production and male nesting success), indicating strong costs of the lingering immunopathology. We show that these substantial sexually-concordant fitness effects of immune response act to align multivariate selection across the sexes, masking the signature of sexual antagonism that acted on morphology alone. Although both sexes experienced costs of fibrosis, the net impacts are unequal because in the two study populations females had higher cestode exposure. To evaluate whether this difference in risk should drive sex-specific immune strategies, we analyze a quantitative genetic model of host immune response to a trophically transmitted parasite. The model and empirical data illustrate how shared costs and benefits of immune response lead to shared evolutionary interests of male and female hosts, despite unequal infection risks across the sexes.
Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length
Authors: Mercadante Dayna L. , Manning Amity L. , Olson Sarah D. 
Published: July 2020

ABSTRACTProper formation and maintenance of the mitotic spindle is required for faithful cell division. While much work has been done to understand the roles of the key molecular components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression. To reflect early spindle formation, we model microtubule dynamics and interactions with major force-generating motors, excluding chromosome interactions that dominate later in mitosis. We directly integrate our experimental data to define and validate the model. We then use simulations to analyze individual force components over time and their relationship to spindle dynamics, making it distinct from previously published models. We show through both model predictions and biological manipulation that rather than achieving and maintaining a constant bipolar spindle length, fluctuations in pole to pole distance occur that coincide with microtubule binding and force generation by cortical dynein. Our model further predicts that high dynein activity is required for spindle bipolarity when kinesin-14 (HSET) activity is also high. Together, our results provide novel insight into the role of cortical dynein in the regulation of spindle bipolarity.SIGNIFICANCEThe mitotic spindle is a biophysical machine that is required for cell division. Here we have paired a modeling approach with experimental data to understand the maintenance and dynamics of a bipolar mitotic spindle in the absence of chromosome interactions. We present novel roles of cortical dynein in mitosis, and demonstrate its requirement for both dynamic changes in spindle length and in antagonizing HSET in bipolar spindle formation. Model outputs predict that cortical dynein activity would be limiting in contexts where HSET activity is high and may be of therapeutic relevance in cancer contexts where HSET is often over expressed.
SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4
Authors: Onodi Fanny , Bonnet-Madin Lucie , Meertens Laurent , Karpf Léa , Poirot Justine , Zhang Shen-Ying , Picard Capucine , Puel Anne , Jouanguy Emmanuelle , Zhang Qian , Le Goff Jérôme , Molina Jean-Michel , Delaugerre Constance , Casanova Jean-Laurent , Amara Ali , Soumelis Vassili 
Published: July 2020

AbstractSeveral studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their interaction with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.