bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Emergence and Long-Term Persistence of HIV-Infected T Cell Clones in Children
Authors: Bale Michael J. , Katusiime Mary Grace , Wells Daria , Wu Xiaolin , Spindler Jonathan , Halvas Elias K. , Cyktor Joshua C. , Wiegand Ann , Shao Wei , Cotton Mark F. , Hughes Stephen H. , Mellors John W. , Coffin John M. , Van Zyl Gert U. , Kearney Mary F. 
Published: September 2020

AbstractLittle is known about the emergence and persistence of HIV-infected T cell clones in perinatally-infected children. We analyzed peripheral blood mononuclear cells for clonal expansion in 11 children who initiated antiretroviral therapy (ART) between 1.8-17.4 months of age and with viremia suppressed for 6-9 years. We obtained 8,662 HIV-1 integration sites from pre-ART and 1,861 sites on ART. Expanded clones of infected cells were detected pre-ART in 10/11 children. In 8 children, infected cell clones detected pre-ART persisted for 6-9 years on ART. A comparison of integration sites in the samples obtained on ART with healthy donor PBMC infectedex-vivoshowed selection for cells with proviruses integrated inBACH2andSTAT5B. Our analyses indicate that, despite marked differences in T cell composition and dynamics between children and adults, HIV-infected cell clones are established early in children, persist for up to 9 years on ART, and can be driven by proviral integration in proto-oncogenes.
TDP-43 stabilizes transcripts encoding stress granule protein G3BP1: potential relevance to ALS/FTD
Authors: Sidibé Hadjara , Khalfallah Yousra , Xiao Shangxi , Gómez Nicolás B. , Tank Elizabeth M.H. , Di Tomasso Geneviève , Bareke Eric , Aulas Anaïs , McKeever Paul M. , Melamed Ze’ev , Destroimaisons Laurie , Deshaies Jade-Emmanuelle , Zinman Lorne , Parker J. Alex , Legault Pascale , Tétreault Martine , Barmada Sami J. , Robertson Janice , Vande Velde Christine 
Published: September 2020

ABSTRACTTDP-43 nuclear depletion and concurrent cytoplasmic accumulation in vulnerable neurons is a hallmark feature of progressive neurodegenerative proteinopathies such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cellular stress signalling and stress granule dynamics are now recognized to play a role in ALS/FTD pathogenesis. Defective stress granule assembly is associated with increased cellular vulnerability and death. G3BP1 (Ras-GAP SH3-domain-binding protein 1) is a critical stress granule assembly factor. Here, we define that TDP-43 stabilizesG3BP1transcripts via direct binding of a highly conservedcisregulatory element within the 3’UTR. Moreover, we showin vitroandin vivothat nuclear TDP-43 depletion is sufficient to reduce G3BP1 protein levels. Finally, we establish thatG3BP1transcripts are reduced in ALS/FTD patient neurons bearing TDP-43 cytoplasmic inclusions/nuclear depletion. Thus, our data suggest that, in ALS/FTD, there is a compromised stress granule response in disease-affected neurons due to impairedG3BP1mRNA stability caused by TDP-43 nuclear depletion. These data implicate TDP-43 and G3BP1 loss of function as contributors to disease.
Generation of glucocorticoid resistant SARS-CoV-2 T-cells for adoptive cell therapy
Authors: Basar Rafet , Uprety Nadima , Ensley Emily , Daher May , Klein Kimberly , Martinez Fernando , Aung Fleur , Shanley Mayra , Hu Bingqian , Gokdemir Elif , Mendt Mayela , Silva Francia Reyes , Acharya Sunil , Laskowski Tamara , Muniz-Feliciano Luis , Banerjee Pinaki , Li Ye , Li Sufang , Garcia Luciana Melo , Lin Paul , Shaim Hila , Yates Sean G. , Marin David , Kaur Indreshpal , Rao Sheetal , Mak Duncan , Lin Angelique , Miao Qi , Dou Jinzhuang , Chen Ken , Champlin Richard , Shpall Elizabeth J. , Rezvani Katayoun 
Published: September 2020

SUMMARYAdoptive cell therapy with viral-specific T cells has been successfully used to treat life-threatening viral infections, supporting the application of this approach against COVID-19. We expanded SARS-CoV-2 T-cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observed that the choice of cytokines modulates the expansion, phenotype and hierarchy of antigenic recognition by SARS-CoV-2 T-cells. Culture with IL-2/4/7 but not other cytokine-driven conditions resulted in >1000 fold expansion in SARS-CoV-2 T-cells with a retained phenotype, function and hierarchy of antigenic recognition when compared to baseline (pre-expansion) samples. Expanded CTLs were directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T-cells could not be efficiently expanded from the peripheral blood of non-exposed controls. Since corticosteroids are used for the management of severe COVID-19, we developed an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing.
SUMOylation regulates protein cargo in Astrocyte-derived small extracellular vesicles
Authors: Fernández Anllely , Méndez Maxs , Santis Octavia , Corvalan Katherine , Gomez Maria-Teresa , Landgraf Peter , Kahne Thilo , Rojas-Fernandez Alejandro , Wyneken Ursula 
Published: September 2020

ABSTRACTRecent studies have described a new mechanism of intercellular communication mediated by various types of extracellular vesicles (EVs). In particular, exosomes are small EVs (sEVs) released to the extracellular environment by the fusion of the endosomal pathway-related multivesicular bodies (containing intraluminal vesicles) with the plasma membrane. sEVs contain a molecular cargo consisting of lipids, proteins, and nucleic acids. However, the loading mechanisms for this complex molecular cargo have not yet been completely elucidated. In that line, the post translational modification SUMO (Small Ubiquitin-like Modifier) has been shown to impact the incorporation of select proteins into sEVs. We therefore decided to investigate whether SUMOylation is a mechanism that defines protein loading to sEVs. In order to investigate the role of SUMOylation in cargo loading into sEVs, we utilized astrocytes, an essential cell type of the central nervous system with homeostatic functions, to study the impact of SUMOylation on the protein cargo of sEVs. Following SUMO overexpression, achieved by transfection of SUMO plasmids or experimental conditions that modulate SUMOylation in primary astrocyte cultures, we detected proteins related to cell division, translation, and transcription by mass-spectrometry. In astrocyte cultures treated with the general SUMOylation inhibitor 2-D08 (2′,3′,4′-trihydroxy-flavone, 2-(2,3,4-Trihydroxyphenyl)-4H-1-Benzopyran-4-one) we observed an increase in the number of sEVs and a decreased amount of protein cargo within them. In turn, in astrocytes treated with the stress hormone corticosterone, we found an increase of SUMO-2 conjugated proteins and sEVs from these cells contained an augmented protein cargo. In this case, the proteins detected with mass-spectrometry were mostly proteins related to protein translation. To test whether astrocyte-derived sEVs obtained in these experimental conditions could modulate protein synthesis in target cells, we incubated primary neurons with astrocyte-derived sEVs. sEVs from corticosterone-treated astrocytes stimulated protein synthesis while no difference was found with sEVs derived from 2-D08-treated astrocytes. Our results show that SUMO conjugation plays a fundamental role in defining the protein cargo of sEVs impacting the physiological function of target cells.
The sugarcane and sorghum kinomes: insights into evolutionary expansion and diversification
Authors: Aono Alexandre Hild , Pimenta Ricardo José Gonzaga , Garcia Ana Letycia Basso , Correr Fernando Henrique , Hosaka Guilherme Kenichi , Carrasco Marishani Marin , Cardoso-Silva Cláudio Benício , Mancini Melina Cristina , Sforça Danilo Augusto , dos Santos Lucas Borges , Nagai James Shiniti , Pinto Luciana Rossini , Landell Marcos Guimarães de Andrade , Carneiro Monalisa Sampaio , Balsalobre Thiago Willian , Quiles Marcos Gonçalves , Pereira Welison Andrade , Margarido Gabriel Rodrigues Alves , de Souza Anete Pereira 
Published: September 2020

AbstractThe protein kinase (PK) superfamily is one of the largest superfamilies in plants and is the core regulator of cellular signaling. Even considering this substantial importance, the kinomes of sugarcane and sorghum have not been profiled. Here we identified and profiled the complete kinomes of the polyploidSaccharum spontaneum(Ssp) andSorghum bicolor(Sbi), a close diploid relative. The Sbi kinome was composed of 1,210 PKs; for Ssp, we identified 2,919 PKs when disregarding duplications and allelic copies, which were related to 1,345 representative gene models. The Ssp and Sbi PKs were grouped into 20 groups and 120 subfamilies and exhibited high compositional similarities and evolutionary divergences. By utilizing the collinearity between these species, this study offers insights about Sbi and Ssp speciation, PK differentiation and selection. We assessed the PK subfamily expression profiles via RNA-Seq, identifying significant similarities between Sbi and Ssp. Moreover, through coexpression networks, we inferred a core structure of kinase interactions with specific key elements. This study is the first to categorize the allele specificity of a kinome and provides a wide reservoir of molecular and genetic information, enhancing the understanding of the evolutionary history of Sbi and Ssp PKs.HighlightThis study describes the catalog of kinase gene family inSaccharum spontaneumandSorghum bicolor, providing a reservoir of molecular features and expression patterns based on RNA-Seq and co-expression networks.
When conflicts get heated, so does the planet: social-climate dynamics under inequality
Authors: Menard Jyler , Bury Thomas M. , Bauch Chris T. , Anand Madhur 
Published: September 2020

AbstractClimate dynamics are inextricably linked to processes in social systems that are highly unequal. This suggests a need for coupled social-climate models that capture pervasive real-world asymmetries in the population distribution of the consequences of anthropogenic climate change and climate (in)action. Here we develop a simple social-climate model with group structure to investigate how anthropogenic climate change and population heterogeneity co-evolve. We find that greater homophily and resource inequality cause an increase in the global peak temperature anomaly by as much as 0.7°C. Also, climate change can structure human populations by driving opinion polarization. Finally, climate mitigation achieved by reducing the cost of mitigation measures paid by individuals tends to be contingent upon socio-economic conditions, whereas policies that achieve communication between different strata of society show climate mitigation benefits across a broad socio-economic regime. We conclude that advancing climate change mitigation efforts can benefit from a social-climate systems perspective.
Description, measurement, and automatic classification of thePlasmodium bergheioocyst morphology during early differentiation
Authors: Recio-Tótoro Benito , Guerrero Adán , Lanz-Mendoza Humberto 
Published: September 2020

AbstractAfter colonization of the mosquito midgut by the malaria parasite,Plasmodiumdifferentiates from an invasive, motile ookinete to a multiplicative, sessile oocyst. Despite their importance in establishing the infection and increasing its population, the morphological transformation associated with these changes in function has been scarcely explored. Oocyst differentiation begins with the formation of a spherical protrusion near the center of the crescent-shaped ookinete. As this protuberance grows, it engulfs the content of the two distal ends, thus rounding the cell. In this work, scrutinized observations of the overall changes in shape, coupled with the migration of the malaria pigment granules and the nucleus into the protuberance, revealed that the movement of the cell content happens in an anteroposterior manner. The resulting data, formalized as morphometric measurements, led to the identification of 5 transitional stages and to the development of a computer training algorithm that automatically classifies them. Since cell differentiation has been associated with redox fluctuations, the classification algorithm was tested with parasites stained with a glutathione-specific fluorescent probe, revealing a redox modulation during differentiation.
Engineering sensitivity and specificity of AraC-based biosensors responsive to triacetic acid lactone and orsellinic acid
Authors: Wang Zhiqing , Doshi Aarti , Chowdhury Ratul , Wang Yixi , Maranas Costas D. , Cirino Patrick C. 
Published: September 2020

AbstractWe previously described the design of triacetic acid lactone (TAL) biosensor “AraC-TAL1”, based on the AraC regulatory protein. While useful as a tool to screen for enhanced TAL biosynthesis, this variant shows elevated background (leaky) expression, poor sensitivity, and relaxed inducer specificity, including responsiveness to orsellinic acid (OA). More sensitive biosensors specific to either TAL or OA can aid in the study and engineering of polyketide synthases that produce these and similar compounds. In this work, we employed a TetA-based dual-selection to isolate new TAL-responsive AraC variants showing reduced background expression and improved TAL sensitivity. To improve TAL specificity, OA was included as a “decoy” ligand during negative selection, resulting in isolation of a TAL biosensor that is inhibited by OA. Finally, to engineer OA-specific AraC variants, the IPRO computational framework was employed, followed by two rounds of directed evolution, resulting in a biosensor with 24-fold improved OA/TAL specificity, relative to AraC-TAL1.
Alpha fluctuations regulate the accrual of visual information to awareness
Authors: Torralba Mireia , Drew Alice , Sabaté San José Alba , Morís Fernández Luis , Soto-Faraco Salvador 
Published: September 2020

AbstractEndogenous brain processes play a paramount role in shaping up perceptual phenomenology. This is illustrated by the alternations experienced by humans (and other animals) when watching perceptually ambiguous, static images. We hypothesised that endogenous alpha fluctuations in the visual cortex pace the accumulation of sensory information leading to perceptual outcomes. Here, we addressed this hypothesis using binocular rivalry combined with visual entrainment and electroencephalography in humans (64 female, 53 male). The results revealed a correlation between the individual frequency of alpha oscillations in the occipital cortex and perceptual alternation rates experienced during binocular rivalry. In subsequent experiments we show that regulating endogenous brain activity via rhythmic entrainment produced corresponding changes in perceptual alternation rate. These changes were observed only in the alpha range but not at lower entrainment frequencies, and were much reduced when using arrhythmic stimulation. Additionally, entraining at frequencies above the alpha range did not result in speeding up perceptual alternation rates. Overall, these findings support the notion that visual information is accumulated via alpha cycles to promote the emergence of conscious perceptual representations. We suggest that models of binocular rivalry incorporating posterior alpha as a pacemaker can provide an important advance in the comprehension of the dynamics of visual awareness.
Discovery of a Novel Polymer for Xeno-free, Long-term Culture of Human Pluripotent Stem Cell Expansion
Authors: Thorpe Jordan , Nasir Aishah , Burroughs Laurence , Meurs Joris , Pijuan-Galito Sara , Irvine Derek J. , Alexander Morgan R. , Denning Chris 
Published: September 2020

AbstractHuman pluripotent stem cells (hPSCs) can be expanded and differentiatedin vitrointo almost any adult tissue cell type, and thus have great potential as a source for cell therapies with biomedical application. In this study, a fully-defined polymer synthetic substrate is identified for hPSC culture in completely defined, xeno-free conditions. This system can overcome the cost, scalability and reproducibility limitations of current hPSC culture strategies, and facilitate large-scale production. A high-throughput, multi-generational polymer microarray platform approach was used to test over 600 unique polymers and rapidly assess hPSC-polymer interactions in combination with the fully defined xeno-free medium, Essential 8TM(E8). This study identifies as novel nanoscale phase separated blend of poly(tricyclodecane-dimethanol diacrylate) and poly(butyl acrylate) (2:1 v/v), which supports long-term expansion of hPSCs and can be readily coated onto standard cultureware. Analysis of cell-polymer interface interactions through mass spectrometry and integrin blocking studies provides novel mechanistic insight into the role of the E8 proteins in promoting integrin-mediated hPSC attachment and maintaining hPSC signaling, including ability to undergo multi-lineage differentiation. This study therefore identifies a novel substrate for long-term serial passaging of hPSCs in serum-free, commercial chemically-defined E8, which provides a promising and economic hPSC expansion platform for clinical-scale application.
Genome-scale phylogenetic analyses confirmOlpidiumas the closest living zoosporic fungus to the non-flagellated, terrestrial fungi
Authors: Chang Ying , Rochon D’Ann , Sekimoto Satoshi , Wang Yan , Chovatia Mansi , Sandor Laura , Salamov Asaf , Grigoriev Igor V. , Stajich Jason E. , Spatafora Joseph W. 
Published: September 2020

AbstractThe zoosporic obligate endoparasites,Olpidium, hold a pivotal position to the reconstruction of the flagellum loss in fungi, one of the key morphological transitions associated with the colonization of land by the early fungi. We generated genome and transcriptome data from non-axenic zoospores ofOlpidium bornovanusand used a metagenome approach to extract phylogenetically informative fungal markers. Our phylogenetic reconstruction strongly supportedOlpidiumas the closest zoosporic relative of the non-flagellated terrestrial fungi. Super-alignment analyses resolvedOlpidiumas sister to the non-flagellated terrestrial fungi, whereas a super-tree approach recovered different placements ofOlpidium, but without strong support. Further investigations detected little conflicting signal among the sampled markers but revealed a potential polytomy in early fungal evolution associated with the branching order amongOlpidium, Zoopagomycota and Mucoromycota. The branches defining the evolutionary relationships of these lineages were characterized by short branch lengths and low phylogenetic content and received equivocal support for alternative phylogenetic hypotheses from individual markers. These nodes were marked by important morphological innovations, including the transition to hyphal growth and the loss of flagellum, which enabled early fungi to explore new niches and resulted in rapid and temporally concurrent Precambrian diversifications of the ancestors of several phyla of fungi.
Endogenous memory reactivation during sleep in humans is clocked by slow oscillation spindle complexes
Authors: Schreiner Thomas , Petzka Marit , Staudigl Tobias , Staresina Bernhard P. 
Published: September 2020

ABSTRACTSleep is thought to support memory consolidation via reactivation of prior experiences, with particular electrophysiological sleep signatures (slow oscillations (SOs) and sleep spindles) gating the information flow between relevant brain areas. However, empirical evidence for a role of endogenous memory reactivation (i.e., without experimentally delivered memory cues) for consolidation in humans is lacking. Here, we devised a paradigm in which participants acquired associative memories before taking a nap. Multivariate decoding was then used to capture endogenous memory reactivation during non-rapid eye movement (NREM) sleep in surface EEG recordings. Our results reveal reactivation of learning material during SO-spindle complexes, with the precision of SO-spindle coupling predicting reactivation strength. Critically, reactivation strength (i.e. classifier evidence in favor of the previously studied stimulus category) in turn predicts the level of consolidation across participants. These results elucidate the memory function of sleep in humans and emphasize the importance of SOs and spindles in clocking endogenous consolidation processes.
True time series of gene expression from multinucleate single cells reveal essential information on the regulatory dynamics of cell differentiation
Authors: Pretschner Anna , Pabel Sophie , Haas Markus , Heiner Monika , Marwan Wolfgang 
Published: September 2020

AbstractDynamics of cell fate decisions are commonly investigated by inferring temporal sequences of gene expression states by assembling snapshots of individual cells where each cell is measured once. Ordering cells according to minimal differences in expression patterns and assuming that differentiation occurs by a sequence of irreversible steps, yields unidirectional, eventually branching Markov chains with a single source node. In an alternative approach, we used multinucleate cells to follow gene expression taking true time series. Assembling state machines, each made from single-cell trajectories, gives a network of highly structured Markov chains of states with different source and sink nodes including cycles, revealing essential information on the dynamics of regulatory events. We argue that the obtained networks depict aspects of the Waddington landscape of cell differentiation and characterize them as reachability graphs that provide the basis for the reconstruction of the underlying gene regulatory network.
Cryo-EM structure of yeast 90S preribosome at 3.4 Å resolution
Authors: Du Yifei , An Weidong , Ye Keqiong 
Published: September 2020

AbstractPreviously, we determined a cryo-EM structure of Saccharomyces cerevisiae 90S preribosome obtained after depletion of the RNA helicase Mtr4 at 4.5 Å resolution (Sun et al., 2017). The 90S preribosome is an early assembly intermediate of small ribosomal subunit. Here, the structure was improved to 3.4 Å resolution and reveals many previously unresolved structures and interactions, in particular around the central domain of 18S rRNA. The central domain adopts a closed conformation in our structure, in contrast to an open conformation in another high-resolution structure of S. cerevisiae 90S. The new model of 90S would serve as a better reference for investigation of the assembly mechanism of small ribosomal subunit.