bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictability of the antigenic evolution of human influenza A H3 viruses
Authors: Aguas R. , Ferguson N.M. 
Published: September 2019

AbstractThe current influenza A antigenic evolution paradigm suggesting that antigenic evolution is highly constrained, with successful new viruses being near optimal at maximizing their antigenic distance from past strains. This begs the question of whether influenza’s antigenic evolution is fundamentally predictable, or if it takes place on a much higher dimensional antigenic space with multiple possible trajectories. We tackle this issue by building a genotype to phenotype map validated on historical hemagglutination inhibition assay data by using machine learning methods. This map uses amino acid physiochemical properties for inference, learning the expected antigenic distance given the differences in polarity and hydrophobicity observed across any two viral sequences, and is thus applicable to newly sampled viruses with previously unseen amino acids. This allows us to accurately blindly predict the antigenic relevance of soon to be vaccine viral strains. We couple the genotype to phenotype map with a molecular evolutionary simulation algorithm to explore the limits of influenza’s antigenic evolution and infer to what extent it is in fact predictable. Although we do uncover some canalization of antigenic trajectories, we find that multiple antigenic lineages are equally viable at any one point in time even though typically only one of those trajectories is actually realized.
Towards Intelligent Intra-cortical BMI (i2BMI): Low-power Neuromorphic Decoders that outperform Kalman Filters
Authors: Shaikh Shoeb , So Rosa , Sibindi Tafadzwa , Libedinsky Camilo , Basu Arindam 
Published: September 2019

AbstractFully implantable wireless intra-cortical Brain Machine Interfaces (iBMI) is one of the most promising next frontiers in the nascent field of neurotechnology. However, scaling the number of channels in such systems by another 10X is difficult due to power and bandwidth requirements of the wireless transmitter. One promising solution for that is to include more processing, up to the decoder, in the implant so that transmission data rate is reduced drastically. Earlier work on neuromorphic decoders only showed classification of discrete states. We present results for continuous state decoding using a low power neuromorphic decoder chip termed Spike-input Extreme Learning Machine (SELMA). We compared SELMA against state of the art Steady State Kalman Filter (SSKF) across two different datasets involving a total of 4 non-human primates (NHPs). Results show at least a 10% or more increase in the fraction of variance accounted for by SELMA over SSKF across the datasets. Furthermore, estimated energy consumption comparison shows SELMA consuming ≈ 9 nJ/update against SSKF’s ≈ 7.4 nJ/update for an iBMI with a 10 degree of freedom control. Thus, SELMA yields better performance against SSKF with a marginal increase in energy consumption paving the way for reducing transmission data rates in future scaled BMI systems.
Sub-Optimal Learning of Tactile-Spatial Predictions in Patients with Complex Regional Pain Syndrome
Authors: Brown Christopher A. , Scholtes Ingrid , Shenker Nicholas , Lee Michael C. 
Published: September 2019

ABSTRACTIn Complex Regional Pain Syndrome (CRPS), tactile sensory deficits have motivated the therapeutic use of sensory discrimination training. However, the hierarchical organisation of the brain is such that low-level sensory processing can be dynamically influenced by higher-level knowledge, e.g. knowledge learnt from statistical regularities in the environment. It is unknown whether the learning of such statistical regularities is impaired in CRPS. Here, we employed a hierarchical Bayesian model of predictive coding to investigate statistical learning of tactile-spatial predictions in CRPS. Using a sensory change-detection task, we manipulated bottom-up (spatial displacement of a tactile stimulus) and top-down (probabilistic structure of occurrence) factors to estimate hierarchies of prediction and prediction error signals, as well as their respective precisions or reliability. Behavioural responses to spatial changes were influenced by both the magnitude of spatial displacement (bottom-up) and learnt probabilities of change (top-down). The Bayesian model revealed that patients’ predictions (of spatial displacements) were found to be less precise, deviating further from the ideal (statistical optimality) compared to healthy controls. This imprecision was less context-dependent, i.e. more enduring across changes in probabilistic context and less finely-tuned to statistics of the environment. This caused greater precision on prediction errors, resulting in predictions that were driven more by momentary spatial changes and less by the history of spatial changes. These results suggest inefficiencies in higher-order statistical learning in CRPS. This may have implications for therapies based on sensory re-training whose effects may be more short-lived if success depends on higher-order learning.
Maternally-transferred thyroid hormones and life-history variation in birds
Authors: Hsu Bin-Yan , Pakanen Veli-Matti , Boner Winnie , Eeva Tapio , Doligez Blandine , Groothuis Ton G.G. , Korpimäki Erkki , Laaksonen Toni , Lelono Asmoro , Monaghan Pat , Sarraude Tom , Tschirren Barbara , Thomson Robert L. , Tolvanen Jere , Vásquez Rodrigo A. , Ruuskanen Suvi 
Published: September 2019

AbstractLife-history traits vary largely across species and several physiological parameters have been proposed to be associated with life-history variation, such as metabolic rates, glucocorticoids, and oxidative stress. Interestingly, the association between thyroid hormones (THs) and life history variation has never been considered, despite a close interaction between THs and these physiological traits. Because of the crucial effects on embryonic development, THs can also induce transgenerational plasticity when transferred to developing offspring, for instance, via egg yolks in birds. In this study, we compiled a unique data set of maternal yolk THs in 34 bird species across 17 families and 6 orders, and tested for associations with various life-history traits. Our phylogenetic mixed models indicated that both concentrations and total amounts of the two most important forms of THs (T3 and T4) were higher in the eggs of migratory species than in those of resident species, and that there were higher total amounts of T3 in the eggs of precocial species than in those of altricial species. However, maternal THs did not show clear associations with any traits of the pace-of-life syndrome, such as developmental duration, growth rate, or lifespan. When taking environmental factors into account, we found that captive species deposited higher TH concentrations and larger amounts in the egg yolks than wild species. These findings suggest that maternal THs are likely involved in the evolution of life-history variation, or vice versa.
Antibody against envelope protein from human endogenous retrovirus activates neutrophils in systemic lupus erythematosus
Authors: Tokuyama Maria , Gunn Bronwyn M. , Venkataraman Arvind , Kong Yong , Kang Insoo , Townsend Michael J. , Costenbader Karen H. , Alter Galit , Iwasaki Akiko 
Published: September 2019

AbstractNeutrophil activation and the formation of neutrophil extracellular trap (NET) are hallmarks of innate immune activation in systemic lupus erythematosus (SLE) and contribute to the systemic interferon signature. Here we report that the expression of an endogenous retrovirus (ERV) locus ERV-K102, encoding an envelope protein, was significantly elevated in SLE patient blood and was correlated with higher interferon status. Induction of ERV-K102 expression most strongly correlated with reduced transcript levels of epigenetic silencing factors. SLE IgG promoted phagocytosis of ERV-K102 envelope protein by neutrophils through immune complex formation. ERV immune complex phagocytosis resulted in subsequent NET formation consisting of DNA, neutrophil elastase, and citrullinated histone H3. Finally, analysis of anti-ERV-K102 IgG in SLE patients showed that IgG2 likely mediates this effect. Together, we identified an immunostimulatory ERV-K envelope protein elevated in SLE that may be a target of SLE IgG and able to promote neutrophil activation.eTOC summaryUsing ERVmap, the authors determined that the expression of ERV-K102 locus was elevated in SLE patient blood and correlated with the interferon signature. The envelope protein encoded by this locus activates human neutrophils through immune complex formation with SLE IgG.
Carbon Assimilation Strategies in Ultrabasic Groundwater: Clues from the Integrated Study of a Serpentinization-Influenced Aquifer
Authors: Seyler L.M. , Brazelton W.J. , McLean C. , Putman L.I. , Hyer A. , Kubo M.D.Y. , Hoehler T. , Cardace D. , Schrenk M.O. 
Published: September 2019

AbstractSerpentinization is a low-temperature metamorphic process by which ultramafic rock chemically reacts with water. These reactions provide energy and materials that may be harnessed by chemosynthetic microbial communities at hydrothermal springs and in the subsurface. However, the biogeochemistry of microbial populations that inhabit these environments are understudied and are complicated by overlapping biotic and abiotic processes. We applied metagenomics, metatranscriptomics, and untargeted metabolomics techniques to environmental samples taken from the Coast Range Ophiolite Microbial Observatory (CROMO), a subsurface observatory consisting of twelve wells drilled into the ultramafic and serpentinite mélange of the Coast Range Ophiolite in California. Using a combination of DNA and RNA sequence data and mass spectrometry data, we determined that several carbon assimilation strategies, including the Calvin-Benson-Bassham cycle, the reverse tricarboxylic acid cycle, the reductive acetyl-CoA pathway, and methylotrophy are used by the microbial communities inhabiting the serpentinite-hosted aquifer. Our data also suggests that the microbial inhabitants of CROMO use products of the serpentinization process, including methane and formate, as carbon sources in a hyperalkaline environment where dissolved inorganic carbon is unavailable.ImportanceThis study describes the metabolic pathways by which microbial communities in a serpentinite-influenced aquifer may produce biomass from the products of serpentinization. Serpentinization is a widespread geochemical process, taking place over large regions of the seafloor, particularly in slow-spreading mid ocean ridge and subduction zone environments. The serpentinization process is implicated in the origin of life on Earth and as a possible environment for the discovery of life on other worlds in our solar system. Because of the difficulty in delineating abiotic and biotic processes in these environments, major questions remain related to microbial contributions to the carbon cycle and physiological adaptation to serpentinite habitats. This research explores multiple mechanisms of carbon assimilation in serpentinite-hosted microbial communities.
Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma
Authors: Herviou Laurie , Izard Fanny , Karmous-Gadacha Ouissem , Gourzones Claire , Bellanger Celine , Desmedt Eva , Ma Anqi , Vincent Laure , Cartron Guillaume , Vanderkerken Karin , Jin Jian , De Bruyne Elke , Grimaud Charlotte , Julien Eric , Moreaux Jérôme 
Published: September 2019

SUMMARYMultiple myeloma (MM) is a malignancy of plasma cells that largely remains incurable. The search for new therapeutic targets is therefore essential. Here we show that a higher expression of the lysine methyltransferase SETD8, which is responsible for histone H4K20 mono-methylation, is an adverse prognosis factor associated with a poor outcome in two cohorts of newly diagnosed patients. Remarkably, primary malignant plasma cells are particularly addicted to SETD8 activity. Indeed, pharmacological inhibition of this enzyme by the chemical compound UNC0379 demonstrated a significantly higher toxicity in MM cells compared to normal cells from the bone marrow microenvironment. Moreover, RNA sequencing and functional studies revealed that SETD8 inhibition induces a mature non-proliferating plasma cell signature and an activation of the p53 canonical pathway, which together leads to an impairment of myeloma cell proliferation and survival. However, UNC0379 treatment triggers a deadly level of replicative stress in p53 deficient MM cells, indicating that the cytotoxicity associated with SETD8 inhibition is independent of the p53 status. Consistent with this, the combination of UNC0379 with the conventional cytotoxic agent melphalan strongly enhances DNA damage and overcomes drug resistance in myeloma cells. Thus, targeting SETD8 could be of therapeutic interest to improve MM treatment in high-risk patients independently of the p53 status.
Novel function of TRIP6, in brain ciliogenesis
Authors: Shukla Shalmali , Urbanek Pavel , Frappart Lucien , Hänold Ronny , Nagel Sigrun , Monajembashi Shamci , Grigaravicius Paulius , Min Woo Kee , Tapias Alicia , Kassel Olivier , Heuer Heike , Wang Zhao-Qi , Ploubidou Aspasia , Herrlich Peter 
Published: September 2019

AbstractTRIP6, a member of the zyxin-family of LIM domain proteins, is a focal adhesion component. trip6 deletion in the mouse revealed, unexpectedly, in view of its ubiquitous expression, a function in the brain: ependymal and choroid plexus epithelial cells were poorly developed, carrying fewer and shorter cilia, and the mice developed hydrocephalus. TRIP6 disruption, via RNAi or inhibition of its homodimerization, in a choroid plexus epithelial cell line, confirmed its function in ciliogenesis. Zyxin-family members carry numerous protein interaction domains. In common with assembly of other multiprotein complexes, ciliogenesis may be facilitated by molecular assembly factors. Super-resolution microscopy demonstrated TRIP6 localization at the pericentriolar material and along the ciliary axoneme. The requirement for homodimerization which doubles its interaction sites, its punctate localization along the axoneme, and its co-localization with other cilia components suggest a scaffold/co-transporter function for TRIP6 in cilia. This is the first discovery of a protein assembly factor essential for mammalian ciliogenesis.
Fingerprints of cancer by persistent homology
Authors: Carpio A. , Bonilla L. L. , Mathews J. C. , Tannenbaum A. R. 
Published: September 2019

AbstractWe have carried out a topological data analysis of gene expressions for different databases based on the Fermat distance between the z scores of different tissue samples. There is a critical value of the filtration parameter at which all clusters collapse in a single one. This critical value for healthy samples is gapless and smaller than that for cancerous ones. After collapse in a single cluster, topological holes persist for larger filtration parameter values in cancerous samples. Barcodes, persistence diagrams and Betti numbers as functions of the filtration parameter are different for different types of cancer and constitute fingerprints thereof.
REPLICCAR II Study: Data Quality Audit in the Paulista Cardiovascular Surgery Registry
Authors: Maria Maglia Orlandi Bianca , VilcaMejia Omar Asdrubal , Goncharov Maxim , Rocha Kenji Nakahara , Bassolli Lucas , Lisboa Luiz AF , Dallan Luis AO , Jatene Fábio B 
Published: September 2019

AbstractBackgroundElectronic health records databases are important sources of data for research and health practice. The aim of this study was to assess the quality of the data in REPLICCAR II, the Brazilian cardiovascular surgery database based in São Paulo State.Study DesignThe REPLICCAR II database contains data from 9 institutions in São Paulo, with more than 700 variables. We audited data entry at 6 months (n=107 records) and 1 year (n=2229 records) after the start of data collection. We present a modified Aggregate Data Quality Score (ADQ) for 30 variables in this analysis.ResultsThe agreement between the data independently entered by a database operator and a researcher was good for categorical data (Cohen κ = 0.70, 95%CI 059, 0.83). For continuous data, the intraclass coefficient was high for all variables, with only 2 of 15 continuous variables having an ICC of less than 0.90. In an indirect audit, 74% of the selected variables (n = 23) showed a good ADQ score, regarding completeness and reliability.ConclusionsData entry in the REPLICCAR II database is satisfactory and can provide accurate and reliable data for research in cardiovascular surgery in Brazil.
Evidence of capacitation in the parasitoid wasp,Nasonia vitripennisand its potential role in sex allocation
Authors: Jones A.R.C. , Mallon E.B. 
Published: September 2019

AbstractThe allocation of resources to the production of one sex or another has been observed in a large variety of animals. Its theoretical basis allows accurate predictions of offspring sex ratios in many species, but the mechanisms by which sex allocation is controlled are poorly understood. Using previously published data we investigated if alternative splicing, combined with differential expression, were involved with sex allocation in the parasitoid wasp,Nasonia vitripennis. We found that sex allocation is not controlled by alternative splicing but changes in gene expression, that were identified to be involved with oviposition, were shown to be similar to those involved in sperm motility, and capacitation. Genes involved in Cholesterol efflux, a key component of capacitation, along with calcium transport, trypsin and MAPKinase activity were regulated in ovipositing wasps. The results show evidence for regulation of sperm motility and of capacitation in an insect which, in the context of the physiology of theN. vitripennisspermatheca, could be important for sex allocation.
Unconscious learning and automatic inhibition are accompanied by frontal theta and sensorimotor interactions
Authors: Isabella Silvia L. , Cheyne J. Allan , Cheyne Douglas 
Published: September 2019

AbstractCognitive control of behavior is often accompanied by theta-band activity in the frontal cortex, and is crucial for overriding habits and producing desired actions. However, the functional role of theta activity in controlled behavior remains to be determined. Here, we used a behavioral task (Isabella et al., 2019) that covertly manipulated the ability to inhibit (and switch) motor responses using a repeating pattern of stimuli that reduced reaction times (RT) to probable over unexpected stimuli, without participants’ awareness of the pattern. We combined this task with concurrent measures of brain activity and pupil diameter (as a measure of cognitive activity) of 16 healthy adults during response preparation and inhibition during changes in stimulus probability. Observed RT provided evidence of pattern learning and pupillometry revealed parametric changes in cognitive activity with stimulus probability. Critically, reliable pupillary effects (Hedge’s g = 1.38) in the absence of RT differences (g = 0.10) indicated that cognitive activity increased without overt changes in behavior (RT). Such increased cognitive activity was accompanied by parametric increases in frontal theta and sensorimotor gamma. In addition, correlation between pre-stimulus beta and pre-response gamma in the motor cortex and post-stimulus frontal theta activity suggest bidirectional interactions between motor and frontal areas. These interactions likely underlie recruitment of preparatory and inhibitory neural activity during rapid motor control. Furthermore, pupillary and frontal theta effects during learned switches demonstrate that increases in inhibitory control of behavior can occur automatically, without conscious awareness.Significance StatementGoal-directed control is crucial for overriding habits and producing desired actions, which can fail during errors and accidents, and may be impaired in addiction, attention-deficit disorders, or dementia. This type of control, including response inhibition, is typically accompanied by frontal theta-band activity. We examined the relationship between frontal theta and response inhibition during unconscious pattern learning. First, we found that frontal activity was sensitive to changes in control and correlated with reaction times. Second, insufficient motor preparation predicted greater frontal activity, reflecting a greater need for control, which in turn predicted greater response-related motor activity. These results link the frontal and motor cortices, providing possible mechanisms for controlled behavior while demonstrating that goal-directed control can proceed automatically and unconsciously.
Nuclear bundle/cable containing actin during yeast meiosis
Authors: Takagi Tomoko , Osumi Masako , Shinohara Akira 
Published: September 2019

AbstractActin polymerizes to form filaments/cables for motility, transport, and structural framework in a cell. Recent studies show that actin polymers are present not only in cytoplasm, but also in nuclei of vertebrate cells, and their formation is induced in response to stress. Here, by electron microscopic observation with rapid freezing and high-pressure freezing, we found a unique bundled structure containing actin in nuclei of budding yeast cells undergoing meiosis. The nuclear bundle/cable during meiosis consists of multiple filaments with a rectangular lattice arrangement often showing “feather-like” appearance. The bundle is immuno-labeled with anti-actin antibody and sensitive to an actin-depolymerizing drug. Like cytoplasmic bundles, nuclear bundles with actin are rarely seen in pre-meiotic cells and spores, and are induced during meiotic prophase-I. The formation of the nuclear bundles/cables is independent of meiotic DNA double-stranded breaks. We speculate that nuclear bundles/cables containing actin play a role in nuclear events during meiotic prophase I.
Prostaglandin D2Signaling is Not Involved in the Recovery of Rat Hindlimb Tendons from Injury
Authors: Sarver Dylan C , Sugg Kristoffer B , Talarek Jeffrey R , Swanson Jacob B , Oliver David J , Hinken Aaron C , Kramer Henning F , Mendias Christopher L 
Published: September 2019

AbstractInjured tendons heal through the formation of a fibrovascular scar that has inferior mechanical properties compared to native tendon tissue. Reducing inflammation that occurs as a result of the injury could limit scar formation and improve functional recovery of tendons. Prostaglandin D2(PGD2) plays an important role in promoting inflammation in some injury responses and chronic disease processes, and the inhibition of PGD2has improved healing and reduced disease burden in animal models and early clinical trials. Based on these findings, we sought to determine the role of PGD2signaling in the healing of injured tendon tissue. We tested the hypothesis that a potent and specific inhibitor of hematopoietic PGD synthase (HPGDS), GSK2894631A, would improve the recovery of tendons of adult male rats following an acute tenotomy and repair. To test this hypothesis, we performed a full-thickness plantaris tendon tenotomy followed by immediate repair and treated rats twice daily with either 0mg/kg, 2mg/kg, or 6mg/kg of GSK2894631A. Tendons were collected either 7 or 21 days after surgical repair, and mechanical properties of tendons were assessed along with RNA sequencing and histology. While there were some differences in gene expression across groups, the targeted inhibition of HPGDS did not impact the functional repair of tendons after injury as HPGDS expression was surprisingly low in injured tendons. These results indicate that PGD2signaling does not appear to be important in modulating the repair of injured tendon tissue.