bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eye tracking-based estimation and compensation of chromatic offsets for multi-wavelength retinal microstimulation with foveal cone precision
Authors: Domdei Niklas , Linden Michael , Reiniger Jenny L. , Holz Frank G. , Harmening Wolf M. 
Published: April 2019

AbstractMulti-wavelength ophthalmic imaging and stimulation of photoreceptor cells requires consideration of chromatic dispersion of the eye, manifesting in longitudinal and transverse chromatic aberrations. Current image-based techniques to measure and correct transverse chromatic aberration (TCA) and the resulting transverse chromatic offset (TCO) in an adaptive optics retinal imaging system are precise, but lack compensation of small but significant shifts in eye position occurring during in vivo testing. Here we present a method that requires only a single measurement of TCO during controlled movements of the eye to map retinal chromatic image shifts to the image space of a pupil camera. After such calibration, TCO can be compensated by continuously monitoring eye position during experimentation and by interpolating correction vectors from a linear fit to the calibration data. The average change rate of TCO per head shift and the correlation between Kappa and the individual foveal TCA are close to the expectations based on a chromatic eye model. Our solution enables continuous correction of TCO with high spatial precision and avoids high light intensities required for re-measuring TCO after eye position changes, which is necessary for foveal cone-targeted psychophysical experimentation.
Development of Pavlovian-to-instrumental transfer (PIT) task to examine the effects of reward-predicting cues on behavioral activation in young adults
Authors: da Costa Raquel Quimas Molina , Furukawa Emi , Hoefle Sebastian , Moll Jorge , Tripp Gail , Mattos Paulo 
Published: April 2019

AbstractThere is a growing recognition that much of human behavior is governed by the presence of classically conditioned cues. The Pavlovian-to-Instrumental Transfer (PIT) paradigm offers a way to measure the effects of classically conditioned stimuli on behavior. In the current study, a novel PIT paradigm was developed for use in conjunction with an fMRI classical conditioning task. This could allow for a measurement of BOLD responses to anticipated rewards, unconfounded by operant responses, while providing a behavioral measure of conditioning effects. Twenty-four healthy young adults completed 1) instrumental training, 2) Pavlovian conditioning, and 3) Transfer test. During instrumental training, participants learned to apply force on a handgrip to win money from slot machines pictured on a computer screen. During Pavlovian conditioning, slot machines appeared with one of two abstract symbols (cues), one symbol was predictive of monetary reward. During the Transfer test, participants again applied force on a handgrip to win more money. This time, slot machines were presented with the Pavlovian cues, but with the outcomes hidden. The results indicated increased effort on the instrumental task, i.e., higher response frequency and greater force, in the presence of a reward-predicting cue. Our findings add to a growing number of studies demonstrating PIT effects in humans. This paradigm was proved to be useful in measuring the effects of a conditioned stimulus on behavioral activation.
The budding yeast heterochromatic protein Sir3 modulates genome-wide gene expression through transient direct contacts with euchromatin
Authors: Bhattacharjee Pritha , Camasses Alain , Galić Hrvoje , Hrgovčić Ana , Demont Lara , Nguyen Linh Thuy , Vasseur Pauline , Radman-Livaja Marta 
Published: April 2019

AbstractThe SIR complex (Silent Information Regulator) is the building block of heterochromatic structures that silence underlying genes. It is well established that the silenced state is epigenetically inherited but it is not known how the SIR complex is maintained through cell divisions in optimal or variable growth conditions. The biological function of heterochromatin located in subtelomeric regions is also unclear since heterochromatin coverage appears to be limited to a few kbps near chromosome ends and the expression of subtelomeric genes is only marginally affected in the absence of the SIR complex. We use a three pronged approach to address these questions. First, nanopore-MetID, an in vivo foot printing technique similar to DamID that uses nanopore sequencing technology, identified over a thousand new transient contacts between Sir3 and euchromatic genes that are not detectable by ChIP-seq and revealed a previously undocumented low-density mode of Sir3 binding to subtelomeric regions that extends 15kbps downstream of subtelomeric SIR nucleation sites. Second, our measurements of genome-wide Sir3 exchange rates after exit from starvation show that heterochromatin is a highly dynamic structure in optimal growth conditions. Third, “spike-in” RNA-seq time course experiments in the same conditions reveal that Sir3 modulates global mRNA levels in correlation with fluctuations in nutrient availability. We now propose that subtelomeric regions serve as Sir3 hubs from which Sir3 is brought over to distal sites down the chromosome arm where it transiently contacts euchromatic genes in its path. We hypothesize that contacts between Sir3 and actively transcribed genes facilitate the removal of stalled transcription complexes and allow for optimal genome-wide transcription, which gives wt cells a competitive advantage oversir3Δcells when nutrients are limited.
Sox1a mediates the ability of the parapineal to impart habenular left-right asymmetry
Authors: Lekk Ingrid , Duboc Véronique , Faro Ana , Nicolaou Stephanos , Blader Patrick , Wilson Stephen W. 
Published: April 2019

AbstractLeft-right asymmetries in the zebrafish habenular nuclei are dependent upon the formation of the parapineal, a unilateral group of neurons that arise from the medially positioned pineal complex. In this study, we show that both the left and right habenula are competent to adopt left-type molecular character and efferent connectivity upon the presence of only a few parapineal cells. This ability to impart left-sided character is lost in parapineal cells lacking Sox1a function, despite the normal specification of the parapineal itself. Precisely timed laser ablation experiments demonstrate that the parapineal influences neurogenesis in the left habenula at early developmental stages as well as neurotransmitter phenotype and efferent connectivity during subsequent stages of habenular differentiation. These studies reveal a tight coordination between the formation of the unilateral parapineal nucleus and emergence of asymmetric habenulae, ensuring that appropriate lateralised character is propagated within left and right-sided circuitry.
Chemical biofilm dislodgement with chelating and reducing agents in comparison to sonication: implications for the diagnosis of implant associated infection
Authors: Karbysheva Svetlana , Butini Maria Eugenia , Di Luca Mariagrazia , Winkler Tobias , Schütz Michael , Trampuz Andrej 
Published: April 2019

AbstractSonication of removed devices improved the microbiological diagnosis of infection. Recently, chemical agents have been investigated for dislodgement of biofilms, including the chelating agent ethylenediaminetetraacetic acid (EDTA) and the reducing agent dithiothreitol (DTT). We compared the efficacy of chemical methods (EDTA and DTT) to sonication for biofilm dislodgement. Staphylococcus epidermidis (ATCC 35984) and Pseudomonas aeruginosa (ATCC 53278) biofilms were grown on porous glass beads for 3 days. After biofilm formation, beads were exposed to 0.9% saline, sonication and/or chemical agents. Quantitative and qualitative biofilm analyses were performed by colony counting (CFU/ml), isothermal microcalorimetry and scanning electron microscopy. The colony counts after treatment with EDTA and DTT were similar to those after exposure to 0.9% saline (6.3, 6.1 and 6.0 log CFU/ml, respectively) for S. epidermidis biofilms, and (5.1, 5.2 and 5.0 log CFU/ml, respectively) for P. aeruginosa biofilm. Sonication detected higher CFU counts (7.5 log CFU/ml) for S. epidermidis; (p<0.05) and 6.5 log for P. aeruginosa biofilm (p <0.05). Concordant results were detected with isothermal microcalorimetry and scanning electron microscopy. In conclusion, the CFU count after treatment of S. epidermidis or P. aeruginosa biofilms with EDTA and DTT was similar to those observed after 0.9% saline used as control. In contrast, sonication was superior to chemical methods for biofilm dislodgment and detection of microorganisms in sonication fluid. In conclusion, our study showed that sonication is superior to chemical method to dislodge bacterial biofilm from artificial surface and should be considered as standard diagnostic method for biofilm detection in implant-associated infections.
Pharmacological inhibition of soluble epoxide hydrolase as a new therapy for Alzheimer’s Disease
Authors: Griñán-Ferré Christian , Codony Sandra , Pujol Eugènia , Yang Jun , Leiva Rosana , Escolano Carmen , Puigoriol-Illamola Dolors , Companys-Alemany Júlia , Corpas Rubén , Sanfeliu Coral , Loza M. Isabel , Brea José , Morisseau Christophe , Hammock Bruce D. , Vázquez Santiago , Pallàs Mercè , Galdeano Carles 
Published: April 2019

AbstractThe inhibition of the enzyme soluble epoxide hydrolase (sEH) has demonstrated clinical therapeutic effects in several peripheral inflammatory-related diseases, with two compounds that have entered clinical trials. However, the role of this enzyme in the neuroinflammation process has been largely neglected. Herein, we disclose the pharmacological validation of sEH as a novel target for the treatment of Alzheimer’s Disease (AD). Of interest, we have found that sEH is upregulated in brains from AD patients. We have evaluated the cognitive impairment and the pathological hallmarks in two models of age-related cognitive decline and AD using three structurally different and potent sEH inhibitors as chemical probes. Our findings supported our expectations on the beneficial effects of central sEH inhibition, regarding of reducing cognitive impairment, tau hyperphosphorylation pathology and the number of amyloid plaques. Interestingly, our results suggest that reduction of inflammation in the brain is a relevant therapeutic strategy for all stages of AD.
Antibiotics select for novel pathways of resistance in biofilms
Authors: Trampari Eleftheria , Holden Emma R , Wickham Gregory J , Ravi Anuradha , Prischi Filippo , de Oliveira Martins Leonardo , Savva George M , Bavro Vassiliy N. , Webber Mark A 
Published: April 2019

AbstractMost bacteria in nature exist in aggregated communities known as biofilms. Bacteria within biofilms are inherently highly resistant to antibiotics. Current understanding of the evolution and mechanisms of antibiotic resistance is largely derived from work from cells in liquid culture and it is unclear whether biofilms adapt and evolve in response to sub-inhibitory concentrations of drugs. Here we used a biofilm evolution model to show that biofilms of a model food borne pathogen,SalmonellaTyphimurium rapidly evolve in response to exposure to three clinically important antibiotics. Whilst the model strongly selected for improved biofilm formation in the absence of any drug, once antibiotics were introduced the need to adapt to the drug was more important than the selection for improved biofilm formation. Adaptation to antibiotic stress imposed a marked cost in biofilm formation, particularly evident for populations exposed to cefotaxime and azithromycin. We identified distinct resistance phenotypes in biofilms compared to corresponding planktonic control cultures and characterised new mechanisms of resistance to cefotaxime and azithromycin. Novel substitutions within the multidrug efflux transporter, AcrB were identified and validated as impacting drug export as well as changes in regulators of this efflux system. There were clear fitness costs identified and associated with different evolutionary trajectories. Our results demonstrate that biofilms adapt rapidly to low concentrations of antibiotics and the mechanisms of adaptation are novel. This work will be a starting point for studies to further examine biofilm specific pathways of adaptation which inform future antibiotic use.
A new approach to crop model calibration: phenotyping plus post-processing
Authors: Casadebaig Pierre , Debaeke Philippe , Wallach Daniel 
Published: April 2019

AbstractCrop models contain a number of genotype-dependent parameters, which need to be estimated for each genotype. This is a major difficulty in crop modeling. We propose a hybrid method for adapting a crop model to new genotypes. The genotype-dependent parameters of the model could be obtained by phenotyping (or gene-based modeling). Then field data for example from variety trials could be used to provide a simple empirical correction to the model, of the form a+b times an environmental variable. This approach combines the advantages of phenotyping, namely that the genotype-specific parameters have a clear meaning and are comparable between genotypes, and the advantages of fitting the model to field data, namely that the corrected model is adapted to a specific target population. It has the advantage of being very simple to apply, and furthermore gives useful information as to which environmental variables are not fully accounted for in the initial model. In this study, this empirical correction is applied to the SUNFLO crop model for sunflower, using field data from a multi-environment trial network. The empirical correction reduced mean squared error (MSE) on the average by 54% for prediction of yield and by 26% for prediction of oil content, compared to the initial model. Most of the improvement came from eliminating bias, with some further improvement from the environmental term in the regression.
Can hot temperatures limit disease transmission? A test of mechanisms in a zooplankton-fungus system
Authors: Shocket Marta S. , Magnante Alexandra , Duffy Meghan A. , Cáceres Carla E. , Hall Spencer R. 
Published: April 2019

ABSTRACTunimodally to temperature, i.e., be maximized at intermediate temperatures and constrained at extreme low and high temperatures. However, empirical evidence linking hot temperatures to decreased transmission in nature remains limited.We tested the hypothesis that hot temperatures constrain transmission in a zooplankton-fungus (Daphnia dentifera-Metschnikowia bicuspidata) disease system where autumnal epidemics typically start after lakes cool from their peak summer temperatures. This pattern suggested that maximally hot summer temperatures could be inhibiting disease spread.Using a series of lab experiments, we examined the effects of high temperatures on five mechanistic components of transmission. We found that (1) high temperatures increased exposure to parasites by speeding up foraging rate but (2) did not alter infection success post-exposure. (3) High temperatures lowered parasite production (due to faster host death and an inferred delay in parasite growth). (4) Parasites made in hot conditions were less infectious to the next host (instilling a parasite ‘rearing’ or ‘trans-host’ effect of temperature during the prior infection). (5) High temperatures in the free-living stage also reduce parasite infectivity, either by killing or harming parasites.We then assembled the five mechanisms into an index of disease spread. The resulting unimodal thermal response was most strongly driven by the rearing effect. Transmission peaked at intermediate-hot temperatures (25-26°C) and then decreased at maximally hot temperatures (30-32°C). However, transmission at these maximally hot temperatures only trended slightly lower than the baseline control (20°C), which easily sustains epidemics in laboratory conditions and in nature. Overall, we conclude that while exposure to hot epilimnetic temperatures does somewhat constrain disease, we lack evidence that this effect fully explains the lack of summer epidemics in this natural system. This work demonstrates the importance of experimentally testing hypothesized mechanisms of thermal constraints on disease transmission. Furthermore, it cautions against drawing conclusions based on field patterns and theory alone.
Development of a KDM6b shRNA conditional knock down mouse model
Authors: Prier Julia E. , Blewitt Marnie E. , Dickins Ross A. , Turner Stephen J. 
Published: April 2019

AbstractAntigen-specific CD8+T cell differentiation in response to infection is associated with specific changes in the chromatin landscape resulting in acquisition of the lineage-specific effector functions required for pathogen clearance. Lysine (K)-specific demethylase 6B (KDM6b) is a histone demethylase that specifically recognizes and removes methyl groups from K27 tri/dimethylation on histone 3. This histone modification is associated with a repressive transcriptional state, or, in combination with the active H3K4me3 mark, a bivalent epigenetic state. Resolution of bivalency at fundamental transcription factor loci has been shown to be a key mechanism for the initiation of CD8+T cell differentiation. To begin to address the role of KDM6b in regulating H3K27me3 demethylation in CD8+T cell responses to infection, a model whereby KDM6b levels can be modulated is needed. To address this, we developed a conditional short hairpin RNA (shRNA) mouse model targeting KDM6b. Here we demonstrate that KDM6b knockdown results in diminished naive, CD4+and virus-specific CD4+and CD8+T cell response in response to influenza A infection. To address the molecular mechanism, we demonstrate that KDM6b knockdown resulted in reduced H3K27me3 removal from theTbx21bivalent promoter, compared to luciferase hairpin controls. Surprisingly, this did not necessarily impact T-BET expression, or resolution of other bivalent transcription factor promoters. These data suggest that KDM6b knockdown resulting in diminished IAV-specific CD8+ T cell responses may reflect a demethylase independent function.
Longitudinal stability of the brain functional connectome is associated with episodic memory performance in aging
Authors: Ousdal Olga Therese , Kaufmann Tobias , Kolskår Knut , Vik Alexandra , Wehling Eike , Lundervold Astri J. , Lundervold Arvid , Westlye Lars T. 
Published: April 2019

AbstractThe brain functional connectome forms a relatively stable and idiosyncratic backbone that can be used for identification or “fingerprinting” of individuals with a high level of accuracy. While previous cross-sectional evidence has demonstrated increased stability and distinctiveness of the brain connectome during the course of childhood and adolescence, less is known regarding the longitudinal stability in middle and old age. Here we collected structural and resting state functional MRI data at two time-points separated by 2-3 years in 75 middle-aged and older adults (age 49-80, SD = ± 6.91 years) which allowed us to assess the long-term stability of the functional connectome. We show that the connectome backbone generally remains stable over a 2-3 year time frame in middle- and old age. Independent of age, cortical volume was associated with the connectome stability of several canonical resting-state networks, suggesting that the connectome backbone relates to the structural integrity of the cortex. Moreover, individual longitudinal stability of subcortical and default mode networks were associated with differences in cross-sectional and longitudinal measures of episodic memory performance, supporting the functional relevance. The findings encourage the use of connectome stability analyses for understanding individual differences in cognitive aging. Furthermore, the observation that age-related changes in episodic memory performance relates to the stability of subcortical and default mode networks, provides new longitudinal evidence for the importance of these networks in maintaining mnemonic processing in old age.
The Israeli Acute Paralysis Virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs
Authors: Acosta-Reyes Francisco , Neupane Ritam , Frank Joachim , Fernández Israel S. 
Published: April 2019

AbstractTheColonyCollapseDisorder or CCD is a multi-faceted syndrome decimating bee populations worldwide[1]. A group of viruses of the widely distributedDicistroviridaefamily have been identified as a causing agent of CCD[2]. This family of viruses employ non-coding RNA sequences, calledInternalRibosomalEntrySite (IRES), to precisely exploit the host machinery for protein production. Using single-particle cryo-electron microscopy (cryo-EM) we have characterized at high resolution how the IRES of the intergenic region of theIsraeliAcuteParalysisVirus (IAPV) captures and redirects translating ribosomes towards viral messengers. Through a series of six structures at nominal resolutions close to 3Å, we could reconstruct the trajectory of IAPV-IRES from an early small subunit recruitment to a final post-translocated state in the ribosome. An early commitment of IRES/ribosome complexes for global pre-translocation mimicry explains the high efficiency observed for this IRES. The presented structures will help guide on-going efforts directed towards fighting CCD through RNA-interference technology [3].
Machine Source Localization ofTursiops truncatusWhistle-like Sounds in a Reverberant Aquatic Environment
Authors: Woodward SF , Reiss D , Magnasco MO 
Published: April 2019

AbstractMost research into bottlenose dolphins’ (Tursiops truncatus’) capacity for communication has centered on tonal calls termedwhistles, in particular individually distinctive contact calls referred to assignature whistles. While “non-signature” whistles exist, and may be important components of bottlenose dolphins’ communicative repertoire, they have not been studied extensively. This is in part due to the difficulty of attributing whistles to specific individuals, a challenge that has limited the study of not only non-signature whistles but the study of general acoustic exchanges among socializing dolphins. In this paper, we propose the first machine-learning-based approach to identifying the source locations of semi-stationary, tonal, whistle-like sounds in a highly reverberant space, specifically a half-cylindrical dolphin pool. We deliver estimated time-difference-of-arrivals (TDOA’s) and normalized cross-correlation values computed from pairs of hydrophone signals to a random forest model for high-feature-volume classification and feature selection, and subsequently deliver the selected features into linear discriminant analysis, linear and quadratic Support Vector Machine (SVM), and Gaussian process models. In our 14-source-location setup, we achieve perfect accuracy in localization by classification and high accuracy in localization by regression (median absolute deviation of 0.66 m, interquartile range of 0.34 m - 1.57 m), with fewer than 10,000 features. By building a parsimonious (minimum-feature) classification tree model for the same task, we show that a minimally sufficient feature set is consistent with the information valued by a strictly geometric, time-difference-of-arrival-based approach to sound source localization. Ultimately, our regression models yielded better accuracy than the established Steered-Response Power (SRP) method when all training data were used, and comparable accuracy along the pool surface when deprived of training data at testing sites; our methods additionally boast improved computation time and the potential for superior localization accuracy in all dimensions with more training data.