bluuebunny/crossref_metadata_2025_split huggingface dataset:
Undaria pinnatifidaexudates trigger shifts in seawater chemistry and microbial communities from Atlantic Patagonian coasts
Authors: Lozada Mariana , Diéguez María C. , García Patricia E. , Bigatti Gregorio , Livore Juan Pablo , Giarratano Erica , Gil Mónica N. , Dionisi Hebe M. 
Published: October 2020

AbstractThe invasive kelpUndaria pinnatifidahas spread from northeastern Asia to temperate coastal environments worldwide, with profound effects on colonized ecosystems. In this work, we analyzed the effect of exudates fromU. pinnatifidaon the chemical and microbial properties of seawater from a semi-enclosed gulf from Atlantic Patagonia. Exudates ofU. pinnatifida,consisting mainly of carbohydrates, were released at a rate of 1.6 ± 0.8 mg C g−1algae day−1, affecting the quality and optical properties of seawater in experimental incubations. Parallel factor analysis based on excitation-emission matrices collected from exudates revealed the presence of two humic-like and one non-humic fluorescent components. Exudate release stimulated microbial growth and polysaccharide degrading activity in seawater. After a 7-day incubation of fresh seawater with the exudates, changes in microbial community structure were analyzed by large-scale 16S rRNA gene amplicon sequencing. Copiotrophic and fermentative genera such asSpirochaeta(Spirochaetes) andPropionigenium(Fusobacteria) increased in the incubations with algal exudates. Genomic potential prediction revealed that the selected bacterial community could have higher ribosome content - an indicator of the potential for reaching higher metabolic rates - and genes for the degradation of complex organic compounds such as polysaccharides and other carbohydrates present in the exudates. Nutrient addition triggered the emergence of other microbial populations with different ecophysiological niches: unclassified Flavobacteriales, unclassified bacteria related to the recently described Phylum Kiritimatiellaeota, as well as potential pathogens such asVibrio(Gammaproteobacteria) andArcobacter(Epsilonproteobacteria), suggesting potential synergistic effects between invasive macroalgae and human activities.
Recurrent Switching Dynamical Systems Models for Multiple Interacting Neural Populations
Authors: Glaser Joshua I. , Whiteway Matthew , Cunningham John P. , Paninski Liam , Linderman Scott W. 
Published: October 2020

AbstractModern recording techniques can generate large-scale measurements of multiple neural populations over extended time periods. However, it remains a challenge to model non-stationary interactions between high-dimensional populations of neurons. To tackle this challenge, we develop recurrent switching linear dynamical systems models for multiple populations. Here, each high-dimensional neural population is represented by a unique set of latent variables, which evolve dynamically in time. Populations interact with each other through this low-dimensional space. We allow the nature of these interactions to change over time by using a discrete set of dynamical states. Additionally, we parameterize these discrete state transition rules to capture which neural populations are responsible for switching between interaction states. To fit the model, we use variational expectation-maximization with a structured mean-field approximation. After validating the model on simulations, we apply it to two different neural datasets: spiking activity from motor areas in a non-human primate, and calcium imaging from neurons in the nematodeC. elegans. In both datasets, the model reveals behaviorally-relevant discrete states with unique inter-population interactions and different populations that predict transitioning between these states.
Selective participation of single cortical neurons in neuronal avalanches
Authors: Bellay Timothy , Shew Woodrow L. , Yu Shan , Falco-Walter Jessica J. , Plenz Dietmar 
Published: October 2020

ABSTRACTNeuronal avalanches are scale-invariant neuronal population activity patterns in cortex that emergein vivoin the awake state andin vitroduring balanced excitation and inhibition. Theory and experiments suggest that avalanches indicate a state of cortex that improves numerous aspects of information processing by allowing for the transient and selective formation of local as well as system-wide spanning neuronal groups. If avalanches are indeed involved with information processing, one might expect that particular single neurons would participate in particular avalanche patterns selectively. Alternatively, all neurons could participate with equal likelihood in each avalanche as would be expected for a population rate code. Distinguishing these hypotheses, however, has been difficult as robust avalanche analysis requires technically challenging measures of their intricate organization in space and time at the population level, while also recording sub- or suprathreshold activity from individual neurons with high temporal resolution. Here we identify repeated avalanches in the ongoing local field potential (LFP) measured with high-density microelectrode arrays in the cortex of awake nonhuman primates and in acute cortex slices from rats. We studied extracellular unit firingin vivoand intracellular responses of pyramidal neuronsin vitro. We found that single neurons participate selectively in specific LFP-based avalanche patterns. Furthermore, we showin vitrothat manipulating the balance of excitation and inhibition abolishes this selectivity. Our results support the view that avalanches represent the selective, scale-invariant formation of neuronal groups in line with the idea of Hebbian cell assemblies underlying cortical information processing.
Structure of the light harvesting 2 complex reveals two carotenoid energy transfer pathways in a photosynthetic bacterium
Authors: Gardiner Alastair T. , Naydenova Katerina , Castro-Hartmann Pablo , Nguyen-Phan Tu C. , Russo Christopher J. , Sader Kasim , Hunter C. Neil , Cogdell Richard J. , Qian Pu 
Published: October 2020

AbstractWe report the 2.4 Å resolution structure of the light harvesting 2 complex (LH2) fromMarichromatium (Mch.) purpuratumdetermined by electron cryo-microscopy. The structure contains a heptameric ring that is unique among all known LH2 structures, explaining the unusual spectroscopic properties of this bacterial antenna complex. Two sets of distinct carotenoids are identified in the structure, and a network of energy transfer pathways from the carotenoids to bacteriochlorophyllamolecules is shown. The geometry imposed by the heptameric ring controls the resonant coupling of the long wavelength energy absorption band. Together, these details reveal key aspects of the assembly and oligomeric form of purple bacterial LH2 complexes that were previously inaccessible by any technique.One Sentence SummaryThe structure of a heptameric LH2 antenna complex reveals new energy transfer pathways and the basis for assembling LH rings.
Thermally tolerant symbionts may explain Caribbean octocoral resilience to heat stress
Authors: Pelosi Jessie , Eaton Katherine M. , Mychajliw Samantha , terHorst Casey P. , Coffroth Mary Alice 
Published: October 2020

AbstractCoral reef ecosystems are under threat from the frequent and severe impacts of anthropogenic climate change, particularly rising sea surface temperatures. The effects of thermal stress may be ameliorated by adaptation and/or acclimation of the host, symbiont, or holobiont (host + symbiont) to increased temperatures. We examined the role of the symbiont in promoting thermal tolerance of the holobiont, usingAntillogorgia bipinnata(octocoral host) andBreviolum antillogorgium(symbiont) as a model system. We identified five distinct genotypes ofB. antillogorgiumfrom symbiont populations isolated fromAntillogorgiacolonies in the Florida Keys. Three symbiont genotypes were cultured and maintained at 26°C (ambient historical temperature) and two were cultured and maintained at 30°C (elevated historical temperature) for two years. Following culturing, we analyzed the growth rate and carrying capacity of each symbiont genotype at both ambient and elevated temperatures in culture (in vitro). All genotypes grew well at both temperatures, indicating thermal tolerance among theseB. antillogorgiumcultures. Prior culturing at the elevated temperature, however, did not result in increased thermal tolerance. We then inoculated juvenileA. bipinnatapolyps with each of the five symbiont genotypes, and reared these polyps at both ambient and elevated temperatures (in hospiteexperiment). All genotypes were able to establish symbioses with polyps in both temperature treatments. Survivorship of polyps at 30°C was significantly lower than survivorship at 26°C, but all treatments had surviving polyps at 56 days post-infection, suggestive of broad thermal tolerance inB. antillogorgium, which may play a part in the increased resilience of Caribbean octocorals during heat stress events.
Role of Udd protein and heterochromatin in transcriptional selection of individual rRNA genes in theDrosophilagermline
Authors: Fefelova Elena A. , Pleshakova Irina M. , Pirogov Sergei A. , Mikhaleva Elena A. , Poltorachenko Valentin A. , Blokh Roman S. , Abramov Yuri A. , Romashin Daniil D. , Gvozdev Vladimir A. , Klenov Mikhail S. 
Published: October 2020

AbstractEukaryotic genomes contain hundreds of nearly identical rRNA genes, many of which are transcriptionally silent. However, the mechanisms of selective regulation of individual rDNA units remain poorly understood. InDrosophila melanogaster, rDNA repeats containing insertions of R1/R2 retrotransposons within the 28S rRNA sequence undergo inactivation. Here we found that rRNA genes with insertions are specifically enriched with H3K9me3 and HP1a repressive marks, but disruption of heterochromatin components only slightly affects their silencing. Intriguingly, the loss of Udd (Under-developed) protein interacting with Pol I transcription initiation complex, causes an upregulation of R2-inserted rDNA copies in germ cells by two orders of magnitude that is accompanied by the reduction of heterochromatin marks. Thus, for the first time we revealed a factor required for distinguishing between active and silent rDNA units to such a large extent. To clarify a relationship between the rDNA transcriptional status and heterochromatin establishment, we showed that inhibition of transcription by actinomycin D increases the level of H3K9me3 mark erasing the epigenetic differences between inserted and uninserted rRNA genes. Altogether, we suggest that Udd coupled with Pol I transcription initiation machinery defines activation or silencing of individual rDNA units, whereas their transcription level consequently dictates their chromatin state.
In vitrogut modeling as a tool for adaptive evolutionary engineering ofLactiplantibacillus plantarum
Authors: Isenring Julia , Geirnaert Annelies , Hall Alex R. , Jans Christoph , Lacroix Christophe , Stevens Marc J.A. 
Published: October 2020

AbstractResearch and marketing of probiotics demand for holistic strain improvement considering both, the biotic and abiotic gut environment. Here we aim to establish the continuousIn vitrocolonic fermentation model PolyFermS as a tool for adaptive evolutionary engineering. Immobilized fecal microbiota from adult donors were steadily cultivated up to 72 days in PolyFermS reactors, providing a long-term compositional and functional stable ecosystem akin to the donor’s gut. Inoculation of the gut microbiota with immobilized or planktonicLactiplantibacillus plantarumNZ3400, a derivative of the probiotic model strain WCFS1, led to successful colonization. Whole genome sequencing of 45 recovered strains revealed mutations in 16 genes involved in signaling, metabolism, transport, and cell surface. Remarkably, mutations in LP_RS14990, LP_RS15205, and intergenic region LP_RS05100<LP_RS05095 were found in recovered strains from different adaptation experiments. Combined addition of the reference strain NZ3400 and each of those mutants to the gut microbiota resulted in increased abundance of the corresponding mutant in PolyFermS microbiota after 10 days, showing the beneficial nature of these mutations. Our data show that the PolyFermS system is a suitable technology to generate adapted mutants for colonization in colonic conditions. Analysis thereof will provide knowledge about factors involved in gut microbiota colonization and persistence.ImportanceImprovement of bacterial strains to specific abiotic environmental factors is broadly used to enhance strain characteristics for processing and product quality. However, there is currently no multidimensional probiotic strain improvement approach for both, abiotic and biotic factors of a colon microbiota. The continuous PolyFermS fermentation model allows stable and reproducible continuous cultivation of colonic microbiota and provides conditions akin to the host gut with high control and easy sampling. This study investigated the suitability of PolyFermS for adaptive evolutionary engineering of a probiotic model organism for lactobacilli,Lactiplantibacillus plantarum, to an adult human colonic microbiota. The application of PolyFermS controlled gut microbiota environment led to adaptive evolution ofL. plantarumstrains for enhanced gut colonization characteristics. This novel tool for strain improvement can be used to reveal relevant factors involved in gut microbiota colonization and develop adapted probiotic strains with enhanced functionality in the gut.
TET2 drives 5hmc marking ofGATA6and epigenetically defines pancreatic ductal adenocarcinoma transcriptional subtypes
Authors: Eyres Michael , Landfredini Simone , Burns Adam , Blake Andrew , Willenbrock Frances , Goldin Robert , hughes Daniel , Hughes Sophie , Thapa Asmita , Vavoulis Dimitris , Hubert Aline , D’Costa Zenobia , Sabbagh Ahmad , Abraham Aswin G. , Blancher Christine , Jones Stephanie , Verrill Clare , Silva Michael , Soonawalla Zahir , Maughan Timothy , Schuh Anna , Mukherjee Somnath , O’Neill Eric 
Published: October 2020

Background and AimsPancreatic ductal adenocarcinoma (PDAC) is characterised by advanced disease stage at presentation, aggressive disease biology and resistance to therapy resulting in extremely poor five-year survival <10%. PDAC is classified into transcriptional subtypes with distinct survival characteristics, although how these arise is not known. Epigenetic deregulation, rather than genetics, has been proposed to underpin progression but exactly why is unclear and hindered by analysis of clinical samples.MethodsGenome-wide epigenetic mapping of DNA modifications 5-hydroxymethylcytosine (5mc) and 5-hydroxymethylcytosine (5hmc) using oxidative bisulphite sequencing (oxBS). Bioinformatics using iCluster and mutational profiling to identify overlap with transcriptional signatures in FFPE from resected patients and confirmation in vivo.ResultsWe find that more aggressive squamous-like PDAC subtypes result from epigenetic inactivation of loci including GATA6 that promote differentiated classical-pancreatic subtypes. We show that squamous-like PDAC transcriptional subtypes are associated with greater loss of 5hmc due to reduced expression of the 5mc-hydroxylase TET2. Furthermore, we find that SMAD4 directly supports TET2 levels in the pancreas and classical-pancreatic tumors and loss of SMAD4 expression is associated reduced 5hmc, GATA6 and squamous-like tumors. Importantly, enhancing TET2 stability using Metformin and VitaminC/ascorbic acid (AA) restores 5hmc and GATA6 levels, reverting squamous-like tumor phenotypes and WNT-dependencein vitroandin vivo.ConclusionsWe identify epigenetic deregulation of pancreatic differentiation as an underpinning event behind the emergence of transcriptomic subtypes in PDAC. Our data shows that restoring epigenetic control increases biomarkers of classical-pancreatic tumors and raises the possibility that combination of Vitamin C and Metformin may prolong survival in patients with squamous-like pancreatic cancer.
Bird size with dinosaur-level cancer defences: can evolutionary lags during miniaturisation explain cancer robustness in birds?
Authors: Erten E. Yagmur , Tollis Marc , Kokko Hanna 
Published: October 2020

AbstractAn increased appreciation of the ubiquity of cancer risk across the tree of life means we also need to understand the more robust cancer defences some species seem to have. Peto’s paradox, the finding that large-bodied species do not suffer from more cancer even if their lives require far more cell divisions than those of small species, can be explained if large size selects for better cancer defences. Since birds live longer than non-flying mammals of an equivalent body size, and birds are descendants of moderate-sized dinosaurs, we ask whether ancestral cancer defence innovations are retained if body size shrinks in an evolutionary lineage. Our model derives selection coefficients and fixation events for gains and losses of cancer defence innovations over macroevolutionary time, based on known relationships between body size, intrinsic cancer risk, extrinsic mortality (modulated by flight ability) and effective population size. We show that evolutionary lags can, under certain assumptions, explain why birds, descendants of relatively large bodied dinosaurs, retain low cancer risk. Counterintuitively, it is possible for a bird to be ‘too robust’ for its own good: excessive cancer suppression can take away from reproductive success. On the other hand, an evolutionary history of good cancer defences may also enable birds to reap the lifespan-increasing benefits of other innovations such as flight.
Fast 3D printing of large-scale biocompatible hydrogel models
Authors: Anandakrishnan Nanditha , Ye Hang , Guo Zipeng , Chen Zhaowei , Mentkowski Kyle I. , Lang Jennifer K. , Rajabian Nika , Andreadis Stelios T. , Ma Zhen , Spernyak Joseph A. , Lovell Jonathan F. , Wang Depeng , Xia Jun , Zhou Chi , Zhao Ruogang 
Published: October 2020

AbstractLarge scale cell-laden hydrogel models hold great promise for tissue repair and organ transplantation, but their fabrication is faced with challenges in achieving clinically-relevant size and hierarchical structures. 3D bioprinting is an emerging technology, but its application in large, solid hydrogel fabrication has been limited by the slow printing speed that can affect the part quality and the biological activity of the encapsulated cells. Here we present a Fast hydrogeL prOjection stereolithogrAphy Technology (FLOAT) that allows the creation of a centimeter-sized, multiscale solid hydrogel model within minutes. Through precisely controlling the photopolymerization condition, we established low suction force-driven, high-velocity flow of the hydrogel prepolymer that supports the continuous replenishment of the prepolymer solution below the curing part and the nonstop part growth. We showed that this process is unique to the hydrogel prepolymer without externally supplemented oxygen. The rapid printing of centimeter-sized hydrogel models using FLOAT was shown to significantly reduce the part deformation and cellular injury caused by the prolonged exposure to the environmental stresses in layer-by-layer based printing methods. Media perfusion in the printed vessel network was shown to promote cell survival and metabolic function in the deep core of the large-sized hydrogel model over long term. The FLOAT is compatible with multiple photocurable hydrogel materials and the printed scaffold supports the endothelialization of prefabricated vascular channels. Together, these studies demonstrate a rapid 3D hydrogel printing method and highlight the potential of this method in the fabrication of large-sized engineered tissue models.
Broad transcriptional dysregulation of brain and choroid plexus cell types with COVID-19
Authors: Yang Andrew C. , Kern Fabian , Losada Patricia M. , Maat Christina A. , Schmartz Georges , Fehlmann Tobias , Schaum Nicholas , Lee Davis P. , Calcuttawala Kruti , Vest Ryan T. , Gate David , Berdnik Daniela , McNerney M. Windy , Channappa Divya , Cobos Inma , Ludwig Nicole , Schulz-Schaeffer Walter J. , Keller Andreas , Wyss-Coray Tony 
Published: October 2020

AbstractThough SARS-CoV-2 primarily targets the respiratory system, it is increasingly appreciated that patients may suffer neurological symptoms of varied severity1–3. However, an unbiased understanding of the molecular processes across brain cell types that could contribute to these symptoms in COVID-19 patients is still missing. Here, we profile 47,678 droplet-based single-nucleus transcriptomes from the frontal cortex and choroid plexus across 10 non-viral, 4 COVID-19, and 1 influenza patient. We complement transcriptomic data with immunohistochemical staining for the presence of SARS-CoV-2. We find that all major cortex parenchymal and choroid plexus cell types are affected transcriptionally with COVID-19. This arises, in part, from SARS-CoV-2 infection of the cortical brain vasculature, meninges, and choroid plexus, stimulating increased inflammatory signaling into the brain. In parallel, peripheral immune cells infiltrate the brain, microglia activate programs mediating the phagocytosis of live neurons, and astrocytes dysregulate genes involved in neurotransmitter homeostasis. Among neurons, layer 2/3 excitatory neurons—evolutionarily expanded in humans4—show a specific downregulation of genes encoding major SNARE and synaptic vesicle components, predicting compromised synaptic transmission. These perturbations are not observed in terminal influenza. Many COVID-19 gene expression changes are shared with those in chronic brain disorders and reside in genetic variants associated with cognitive function, schizophrenia, and depression. Our findings and public dataset provide a molecular framework and new opportunities to understand COVID-19 related neurological disease.
Human bronchial epithelial cell-derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of TGF-β-WNT crosstalk
Authors: Kadota Tsukasa , Fujita Yu , Araya Jun , Watanabe Naoaki , Fujimoto Shota , Kawamoto Hironori , Minagawa Shunsuke , Hara Hiromichi , Ohtsuka Takashi , Yamamoto Yusuke , Kuwano Kazuyoshi , Ochiya Takahiro 
Published: October 2020

AbstractIdiopathic pulmonary fibrosis (IPF) is characterized by devastating and progressive lung parenchymal fibrosis, resulting in poor patient prognosis. An aberrant recapitulation of developmental lung gene expression, including genes for transforming growth factor (TGF)-β and WNT, has been widely implicated in the pathogenic IPF wound healing process that results from repetitive alveolar epithelial injury. Extracellular vesicles (EVs) have been shown to carry bioactive molecules and to be involved in various physiological and pathological processes. Here, we demonstrate that, by attenuating WNT signaling, human bronchial epithelial cell-derived EVs (HBEC EVs) inhibit TGF-β mediated induction of both myofibroblast differentiation and lung epithelial cellular senescence. This effect of HBEC EVs is more pronounced than that observed with mesenchymal stem cell-derived EVs. Mechanistically, the HBEC EV microRNA (miRNA) cargo is primarily responsible for attenuating both myofibroblast differentiation and cellular senescence. This attenuation occurs via inhibition of canonical and non-canonical WNT signaling pathways. Among enriched miRNA species present in HBEC EVs, miR-16, miR-26a, miR-26b, miR-141, miR-148a, and miR-200a are mechanistically involved in reducing WNT5A and WNT10B expression in LFs, and in reducing WNT3A, WNT5A, and WNT10B expression in HBECs. Mouse models utilizing intratracheal administration of EVs demonstrate efficient attenuation of bleomycin-induced lung fibrosis development accompanied by reduced expression of both β-catenin and markers of cellular senescence. These findings indicate that EVs derived from normal resident lung HBECs may possess anti-fibrotic properties. They further suggest that, via miRNA-mediated inhibition of TGF-β-WNT crosstalk, HBEC EVs administration can be a promising anti-fibrotic modality of treatment for IPF.