bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impacts of radiation on the bacterial and fungal microbiome of small mammals in the Chernobyl Exclusion Zone
Authors: Antwis Rachael E. , Beresford Nicholas A. , Jackson Joseph A. , Fawkes Ross , Barnett Catherine L. , Potter Elaine , Walker Lee , Gaschak Sergey , Wood Michael D. 
Published: May 2020

ABSTRACTEnvironmental impacts of the 1986 Chernobyl Nuclear Power Plant accident are much debated, but the effects of radiation on host microbiomes has received little attention to date. We present the first analysis of small mammal gut microbiome from the Chernobyl Exclusion Zone in relation to total absorbed dose rate and including caecum as well as faeces sample. The associations between microbiome communities and radiation exposure varied between host species. Associations between microbiome and radiation was different for analyses based on ambient versus total weighted absorbed dose rates. We found considerable variation between patterns for faecal and gut samples of bank voles, suggesting faecal samples are not an accurate indicator of gut composition. For bank vole guts, associations between radiation and bacterial community composition were robust against geographical and habitat variation. We found limited associations between radiation and fungal communities. Host physiological mechanisms or environmental factors may be driving these patterns.
Xylose Metabolism and the Effect of Oxidative Stress on Lipid and Carotenoid Production in Rhodotorula toruloides: Insights for Future Biorefinery
Authors: Pinheiro Marina Julio , Bonturi Nemailla , Belouah Isma , Miranda Everson Alves , Lahtvee Petri-Jaan 
Published: May 2020

AbstractThe use of cell factories to convert sugars from lignocellulosic biomass into chemicals in which oleochemicals and food additives, such as carotenoids, is essential for the shift towards sustainable processes. Rhodotorula toruloides is a yeast that naturally metabolises a wide range of substrates, including lignocellulosic hydrolysates, and converts them into lipids and carotenoids. In this study, xylose, the main component of hemicellulose, was used as the sole substrate for R. toruloides, and a detailed physiology characterisation combined with absolute proteomics and genome-scale metabolic models was carried out to understand the regulation of lipid and carotenoid production. To improve these productions, oxidative stress was induced by hydrogen peroxide and light irradiation and further enhanced by adaptive laboratory evolution. Based on the online measurements of growth and CO2 excretion, three distinct growth phases were identified during batch cultivations. The intracellular flux estimations correlated well with the measured protein levels and demonstrated improved NADPH regeneration, phosphoketolase activity and reduced beta-oxidation, correlating with increasing lipid yields. Light irradiation resulted in 70% higher carotenoid and 40% higher lipid yields. The presence of hydrogen peroxide did not affect the carotenoid yield but culminated in the highest lipid yield of 0.65 g/gDCW. The adapted strain showed improved fitness and 2.3-fold higher carotenoid yield than the parental strain. This work presented a holistic view of xylose conversion into microbial oil and carotenoids by R. toruloides for further cost-effective and renewable production of these molecules.
obaDIA: one-step biological analysis pipeline for data-independent acquisition and other quantitative proteomics data
Authors: Yan Jun , Zhai Hongning , Zhu Ling , Sa Sasha , Ding Xiaojun 
Published: May 2020

AbstractMotivationData mining and data quality evaluation are indispensable constituents of quantitative proteomics, but few integrated tools available.ResultsWe introduced obaDIA, a one-step pipeline to generate visualizable and comprehensive results for quantitative proteomics data. obaDIA supports fragment-level, peptide-level and protein-level abundance matrices from DIA technique, as well as protein-level abundance matrices from other quantitative proteomic techniques. The result contains abundance matrix statistics, differential expression analysis, protein functional annotation and enrichment analysis. Additionally, enrichment strategies which use total proteins or expressed proteins as background are optional, and HTML based interactive visualization for differentially expressed proteins in the KEGG pathway is offered, which helps biological significance mining. In short, obaDIA is an automatic tool for bioinformatics analysis for quantitative proteomics.AvailabilityobaDIA is freely available fromhttps://github.com/yjthu/obaDIA.git.Contactdingxiaojun@e-omics.com
Recovery of Consciousness and Cognition after General Anesthesia in Humans
Authors: Mashour George A. , Palanca Ben J.A. , Basner Mathias , Li Duan , Wang Wei , Blain-Moraes Stefanie , Lin Nan , Maier Kaitlyn , Muench Maxwell , Tarnal Vijay , Vanini Giancarlo , Ochroch E. Andrew , Hogg Rosemary , Schwarz Marlon , Maybrier Hannah , Hardie Randall , Janke Ellen , Golmirzaie Goodarz , Picton Paul , McKinstry-Wu Andrew , Avidan Michael S. , Kelz Max B. 
Published: May 2020

AbstractUnderstanding how consciousness and cognitive function return after a major perturbation is important clinically and neurobiologically. To address this question, we conducted a three-center study of 30 healthy humans receiving general anesthesia at clinically relevant doses for three hours. We administered a pre- and post-anesthetic battery of neurocognitive tests, recorded continuous electroencephalography to assess cortical dynamics, and monitored sleep-wake activity before and following anesthetic exposure. We hypothesized that cognitive reconstitution would be a process that evolved over time in the following sequence: attention, complex scanning and tracking, working memory, and executive function. Contrary to our hypothesis, executive function returned first and electroencephalographic analyses revealed that frontal cortical dynamics recovered faster than posterior cortical dynamics. Furthermore, actigraphy indicated normal sleep-wake patterns in the post-anesthetic period. These recovery patterns of higher cognitive function and arousal states suggest that the healthy human brain is resilient to the effects of deep general anesthesia.
Hippocampal subfield volumes across the healthy lifespan and the effects of MR sequence on estimates
Authors: Bussy Aurelie , Plitman Eric , Patel Raihaan , Tullo Stephanie , Salaciak Alyssa , Bedford Saashi A. , Farzin Sarah , Béland Marie-Lise , Valiquette Vanessa , Kazazian Christina , Tardif Christine , Devenyi Gabriel A. , Chakravarty Mallar 
Published: May 2020

AbstractThe hippocampus has been extensively studied in various neuropsychiatric disorders throughout the lifespan. However, inconsistent results have been reported with respect to which subfield volumes are most related to age. Here, we investigate whether these discrepancies may be explained by experimental design differences that exist between studies. Multiple datasets were used to collect 1690 magnetic resonance scans from healthy individuals aged 18-95 years old. Standard T1-weighted (T1w; MPRAGE sequence, 1 mm3voxels), high-resolution T2-weighted (T2w; SPACE sequence, 0.64 mm3voxels) and slab T2-weighted (Slab; 2D turbo spin echo, 0.4 x 0.4 x 2 mm3voxels) images were acquired. The MAGeT Brain algorithm was used for segmentation of the hippocampal grey matter (GM) subfields and peri-hippocampal white matter (WM) subregions. Linear mixed-effect models and Akaike information criterion were used to examine linear, second or third order natural splines relationship between hippocampal volumes and age. We demonstrated that stratum radiatum/lacunosum/moleculare and fornix subregions expressed the highest relative volumetric decrease, while the cornus ammonis 1 presented a relative volumetric preservation of its volume with age. We also found that volumes extracted from slab images were often underestimated and demonstrated different age-related relationships compared to volumes extracted from T1w and T2w images. The current work suggests that although T1w, T2w and slab derived subfield volumetric outputs are largely homologous, modality choice plays a meaningful role in the volumetric estimation of the hippocampal subfields.
Toxin-like neuropeptides in the sea anemoneNematostellaunravel recruitment from the nervous system to venom
Authors: Sachkova Maria Y. , Landau Morani , Surm Joachim M. , Macrander Jason , Singer Shir , Reitzel Adam M. , Moran Yehu 
Published: May 2020

AbstractThe sea anemoneNematostella vectensis(Anthozoa, Cnidaria) is a powerful model system for characterizing the evolution of genes functioning in venom and nervous systems. Despite being an example for evolutionary novelty, the evolutionary origin of most toxins remains unknown. Here we report the first bona fide case of protein recruitment from the cnidarian nervous to venom system. The ShK-like1 peptide has ShKT cysteine motif, is lethal for fish larvae and packaged into nematocysts, the cnidarian venom-producing stinging capsules. Thus, ShK-like1 is a toxic venom component. Its paralog, ShK-like2, is a neuropeptide localized to neurons and is involved in development. Interestingly, both peptides exhibit similarities in their functional activities: both of them provoke contraction inNematostellapolyps and are toxic to fish. Because ShK-like2 but not ShK-like1 is conserved throughout sea anemone phylogeny, we conclude that the two paralogs originated due to aNematostella-specific duplication of a ShK-like2 ancestor, a neuropeptide-encoding gene, followed by diversification and partial functional specialization. Strikingly, ShK-like2 is represented by two gene isoforms controlled by alternative promoters conferring regulatory flexibility throughout development. Additionally, we characterized the expression patterns of four other peptides with structural similarities to studied venom components, and revealed their unexpected neuronal localization. Thus, we employed genomics, transcriptomics and functional approaches to reveal one new venom component, five neuropeptides with two different cysteine motifs and an evolutionary pathway from nervous to venom system in Cnidaria.
Auditory Corticothalamic Neurons are Recruited by Motor Preparatory Inputs
Authors: Clayton Kameron K. , Williamson Ross S. , Hancock Kenneth E. , Hackett Troy , Polley Daniel B 
Published: May 2020

SUMMARYOptogenetic activation ofNtsr1+ layer 6 corticothalamic (L6 CT) neurons modulates thalamocortical sensory processing and perception for hundreds of milliseconds following laser offset. Naturally occurring sources of extrasensory inputs that could recruit L6 CTs prior to upcoming sensory stimuli have not been identified. Here, we found that 100% of L6 CTs in mouse primary auditory cortex (A1) expressed FoxP2, a protein marker found in brain areas that coordinate sensory inputs with movement. To test the idea that motor preparatory inputs could be a natural extrasensory activator of L6 CTs, we combined quantitative videography, optogenetically targeted single unit recordings, and two-photon imaging during self-initiated behavior. We found that A1 L6 CTs were activated hundreds of milliseconds prior to orofacial movements, but not whole-body movements associated with locomotion. These findings identify new local circuit arrangements for routing motor corollary discharge into A1 and suggest new roles for CT neurons in active sensing.
Cell type-specific proteogenomic signal diffusion for integrating multi-omics data predicts novel schizophrenia risk genes
Authors: Torshizi Abolfazl Doostparast , Duan Jubao , Wang Kai 
Published: May 2020

AbstractAccumulation of diverse types of omics data on schizophrenia (SCZ) requires a systems approach to jointly modeling the interplay between genome, transcriptome and proteome. Proteome dynamics, as the definitive cellular machinery in human body, has been lagging behind the research on genome/transcriptome in the context of SCZ, both at tissue and single-cell resolution. We introduce a Markov Affinity-based Proteogenomic Signal Diffusion (MAPSD) method to model intra-cellular protein trafficking paradigms and tissue-wise single-cell protein abundances. MAPSD integrates multi-omics data to amplify the signals at SCZ risk loci with small effect sizes, and reveal convergent disease-associated gene modules in the brain interactome as well as more than 130 tissue/cell-type combinations. We predicted a set of high-confidence SCZ risk genes, the majority of which are not directly connected to SCZ susceptibility risk genes. We characterized the subcellular localization of proteins encoded by candidate SCZ risk genes in various brain regions, and illustrated that most are enriched in neuronal and Purkinje cells in cerebral cortex. We demonstrated how the identified gene set may be involved in different developmental stages of the brain, how they alter SCZ-related biological pathways, and how they can be effectively leveraged for drug repurposing. MAPSD can be applied to other polygenic diseases, yet our case study on SCZ signifies how tissue-adjusted protein-protein interaction networks can assist in generating deeper insights into the orchestration of polygenic diseases.
Frizzled-7 Identifies Platinum Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis
Authors: Wang Yinu , Zhao Guangyuan , Condello Salvatore , Huang Hao , Cardenas Horacio , Tanner Edward , Wei Jian-Jun , Ji Yanrong , Li Junjie , Tan Yuying , Davuluri Ramana , Cheng Ji-Xin , Matei Daniela 
Published: May 2020

AbstractDefining traits of platinum tolerant cancer cells could expose new treatment vulnerabilities. Here, new markers associated with platinum tolerant cells and tumors were identified by usingin vitroandin vivoovarian cancer (OC) models treated repetitively with carboplatin and validated in human specimens. Platinum-tolerant cells and tumors were found to be enriched in ALDH (+) cells, formed more spheroids, and expressed increased levels of stemness-related transcription factors compared to parental cells. Additionally, platinum-tolerant cells and tumors highly expressed the Wnt receptor,Frizzled 7(FZD7). FZD7 knock down improved sensitivity to platinum, decreased spheroid formation, and delayed tumor initiation. The molecular signature distinguishing FZD7(+) from FZD7(-) cells includedepithelial-to-mesenchymal (EMT), stemness, andoxidative phosphorylationenriched gene sets. Overexpression ofFZD7activated the oncogenic factorTp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protects cells from chemotherapy-induced oxidative stress. FZD7(+) platinum-tolerant OC cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors.FZD7, Tp63and glutathione metabolism gene sets were strongly correlated in the OC Tumor Cancer Genome Atlas (TCGA) database and in human OC specimens residual after chemotherapy. These results support the existence of a platinum-tolerant cell population with partial stem cell features, characterized by FZD7 expression and dependent on FZD7-β-catenin-Tp63-GPX4 pathway for survival. The findings reveal a novel therapeutic vulnerability of platinum tolerant cancer cells and provide new insight into a potential “persister cancer cell” phenotype.
Silk Fibroin as an Additive for Cell-Free Protein Synthesis
Authors: Lee Marilyn S. , Hung Chia-Suei , Phillips Daniel A. , Buck Chelsea C. , Gupta Maneesh K. , Lux Matthew W. 
Published: May 2020

AbstractCell-free systems contain many proteins and metabolites required for complex functions such as transcription and translation or multi-step metabolic conversions. Research into expanding the delivery of these systems by drying or by embedding into other materials is enabling new applications in sensing, point-of-need manufacturing, and responsive materials. Meanwhile, silk fibroin from the silk worm,Bombyx mori, has received attention as a protective additive for dried enzyme formulations and as a material to build biocompatible hydrogels for controlled localization or delivery of biomolecular cargoes. In this work, we explore the effects of silk fibroin as an additive in cell-free protein synthesis (CFPS) reactions. Impacts of silk fibroin on CFPS activity and stability after drying, as well as the potential for incorporation of CFPS into hydrogels of crosslinked silk fibroin are assessed. We find that simple addition of silk fibroin increased productivity of the CFPS reactions by up to 42%, which we attribute to macromolecular crowding effects. However, we did not find evidence that silk fibroin provides a protective effects after drying as previously described for purified enzymes. Further, the enzymatic crosslinking transformations of silk fibroin typically used to form hydrogels are inhibited in the presence of the CFPS reaction mixture. Crosslinking attempts did not impact CFPS activity, but did yield localized protein aggregates rather than a hydrogel. We discuss the mechanisms at play in these results and how the silk fibroin-CFPS system might be improved for the design of cell-free devices.
Polymorphisms in STING affect human innate immune responses to poxviruses
Authors: Kennedy Richard B. , Haralambieva Iana H. , Ovsyannikova Inna G. , Voigt Emily A. , Larrabee Beth R. , Schaid Daniel J. , Zimmermann Michael T. , Oberg Ann L. , Poland Gregory A. 
Published: May 2020

AbstractWe conducted a large genome-wide association study (GWAS) of the immune responses to primary smallpox vaccination in a combined cohort of > 1,600 subjects. We identified a cluster of SNPs on chromosome 5 (5q31.2) that were significantly associated (p-value: 1.3 × 10−12– 1.5×10−36) with IFNα response toin vitropoxvirus stimulation. Examination of these SNPs led to the functional testing of rs1131769, a non-synonymous SNP inTMEM173causing an Arg-to-His change at position 232 in the STING protein—a major regulator of innate immune responses to viral infections. Our findings demonstrate important functional differences between the two alleles, where the major allele (R232) more effectively induces IFNα secretion. Molecular modeling of both alleles identified altered ligand binding characteristics between the two variants, providing a potential mechanism underlying differences in inter-individual responses to poxvirus vaccination. Our data demonstrate that possession of the H232 variant impairs STING-mediated innate immunity to poxviruses. These results clarify prior studies evaluating functional effects of genetic variants inTMEM173and provide novel data regarding genetic control of poxvirus immunity.Contribution to the FieldHere we report that a single nucleotide non-synonymous polymorphism in theTMEM173gene encodes for a STING variant conferring a reduced IFN stimulated response compared to wild type. Our results suggest that, upon binding of the STING H232 variant to its ligand, activation of downstream signaling proteins is impaired, resulting in decreased production of IFNα and a weaker interferon-stimulated gene response. Molecular modeling indicates that the diminished functional activity of this variant is likely due to an altered physical structure of the STING protein. STING controls the innate, type I IFN response to double-stranded DNA and cyclic dinucleotides. Individuals with the H232 variant of STING have a much weaker innate immune response to vaccinia virus. Our data help resolve ongoing controversies regarding the role of genetic variants in STING function. Because STING plays an important role in our immune response to DNA viruses and bacteria, our results can be used to predict who will and will not respond to vaccines and treatments, and to design more effective vaccine candidates. Given the role of the STING protein in innate responses to DNA viruses and bacterial pathogens, these data may also be useful in developing novel treatment options for multiple infectious diseases.
Homeostatic plasticity triggered by rod photoreceptor degenerative disease is associated with maintenance of sensitive night vision
Authors: Leinonen Henri , Pham Nguyen C , Boyd Taylor , Santoso Johanes , Palczewski Krzysztof , Vinberg Frans 
Published: May 2020

ABSTRACTNeuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cell dendrites expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed these issues in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network reminiscent of the neurodevelopmental state as well as potentiation of rod – rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. The results implicate retinal adaptation leading to persistent visual function during photoreceptor degenerative disease.
Benchmarking Risk Predictions and Uncertainties in the NSCR Model of GCR Cancer Risks with Revised Low LET Risk Coefficients
Authors: Cucinotta Francis A. , Cacao Eliedonna , Kim Myung-Hee Y. , Saganti Premkumar B. 
Published: May 2020

AbstractWe report on the contributions of model factors that appear in fatal cancer risk projection models to the overall uncertainty in cancer risks predictions for exposures to galactic cosmic ray (GCR) in deep space. Annual GCR exposures to astronauts at solar minimum are considered. Uncertainties in low LET risk coefficients, dose and dose-rate modifiers, quality factors (QFs), space radiation organ doses, non-targeted effects (NTE) and increased tumor lethality at high LET compared to low LET radiation are considered. For the low LET reference radiation parameters we use a revised assessment of excess relative risk (ERR) and excess additive risk (EAR) for radiation induced cancers in the Life-Span Studies (LSS) of the Atomic bomb survivors that was recently reported, and also consider ERR estimates for males from the International Study of Nuclear Workers (INWORKS). For 45-y old females at mission age the risk of exposure induced death (REID) per year and 95% confidence intervals is predicted as 1.6% [0.71, 1.63] without QF uncertainties and 1.64% [0.69, 4.06] with QF uncertainties. However, fatal risk predictions increase to 5.83% [2.56, 9.7] with non-targeted effects. For males a comparison application to GCR using LSS or INWORKS lead to predictions of 1.24% [0.58, 3.14] and 2.45% [1.23, 5.9] without NTEs. The major conclusion of our report is that high LET risk prediction uncertainties due to QFs parameters, NTEs, and possible increase lethality at high LET are dominant contributions to GCR uncertainties and should be the focus of space radiation research.
GalaxyCloudRunner: enhancing scalable computing for Galaxy
Authors: Goonasekera N , Mahmoud A , Chilton J , Afgan E 
Published: May 2020

AbstractSummaryThe existence of more than 100 public Galaxy servers with service quotas is indicative of the need for an increased availability of compute resources for Galaxy to use. The GalaxyCloudRunner enables a Galaxy server to easily expand its available compute capacity by sending user jobs to cloud resources. User jobs are routed to the acquired resources based on a set of configurable rules and the resources can be dynamically acquired from any of 4 popular cloud providers (AWS, Azure, GCP, or OpenStack) in an automated fashion.Availability and implementationGalaxyCloudRunner is implemented in Python and leverages Docker containers. The source code is MIT licensed and available athttps://github.com/cloudve/galaxycloudrunner. The documentation is available athttp://gcr.cloudve.org/.ContactEnis Afgan (enis.afgan@jhu.edu)Supplementary informationNone