bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Dynamics of the Salicylic Acid Response and its Interplay with the Jasmonic Acid Pathway
Authors: Hickman Richard , Mendes Marciel Pereira , Van Verk Marcel C. , Van Dijken Anja J.H. , Di Sora Jacopo , Denby Katherine , Pieterse Corné M.J. , Van Wees Saskia C.M. 
Published: August 2019

AbstractThe phytohormone salicylic acid (SA) is a central regulator of plant immunity. Antagonistic and synergistic actions between SA and other defense-associated hormones like jasmonic acid (JA) play key roles in determining the outcome of the plant immune response. To obtain a deeper understanding of SA-mediated transcriptional reprogramming and SA/JA crosstalk, we generated a high-resolution time series of gene expression from Arabidopsis leaves treated with SA alone and a combination of SA and methyl JA (MeJA), sampled at 14 time points over a 16-h period. We found that approximately one-third of the Arabidopsis genome was differentially expressed in response to SA, and temporal changes in gene expression could be partitioned into 45 distinct clusters of process-specific coregulated genes, linked to specific cis-regulatory elements and binding of transcription factors (TFs). Integration of our expression data with information on TF-DNA binding allowed us to generate a dynamic gene regulatory network model of the SA response, recovering known regulators and identifying novel ones. We found that 12% of SA-responsive genes and 69% of the MeJA-responsive genes exhibited antagonistic or synergistic expression levels in the combination treatment. Multi-condition co-clustering of the single- and combined-hormone expression profiles predicted underlying regulatory mechanisms in signal integration. Finally, we identified the TFs ANAC061 and ANAC090 as negative regulators of SA pathway genes and defense against biotrophic pathogens. Collectively, our data provide an unprecedented level of detail about transcriptional changes during the SA response and SA/JA crosstalk, serving as a valuable resource for systems-level network studies and functional plant defense studies.
Analytical characterization of Parylene-C degradation mechanisms on Utah arrays: evaluation of in vitro Reactive Accelerated Aging model compared to multiyearin vivoimplantation
Authors: Caldwell Ryan , Street Matthew G. , Sharma Rohit , Takmakov Pavel , Baker Brian , Rieth Loren 
Published: August 2019

AbstractImplantable neural microelectrodes are integral components of neuroprosthetic technologies and can transform treatments for many neural-mediated disorders. However, dielectric material degradation during long-term (> 1 year) indwelling periods restricts device functional lifetimes to a few years. This comprehensive work carefully investigatesin vivomaterial degradation and also explores the ability ofin vitroReactive Accelerated Aging (RAA) to evaluate implant stability. Parylene C-coated Utah electrode arrays (UEAs) implanted in feline peripheral nerve for 3.25 years were explanted and compared to RAA-processed devices, aged in phosphate buffered saline (PBS) + 20 mM H2O2at either 67 or 87 °C (28 or 7 days, respectively). Electron microscopy revealed similar physical damage characteristics between explants and RAA (87° C) devices. Parylene C degradation was overwhelmingly apparent for UEAs from both RAA cohorts. Controls aged in PBS alone displayed almost no damage. Spectroscopic characterization (EDX, XPS, FTIR) found clear indications of oxidation and chlorine abstraction for parylene C agedin vivo. Whilein vitroaging was also accompanied by signs of oxidation, changes in the chemistryin vivoandin vitrowere statistically different. Analysis of RAA- aged devices identified UEA fabrication approaches that may greatly improve device resistance to degradation. This work underscores the need for an improved understanding ofin vivodamage mechanisms, to facilitate the critical need for representativein vitroaccelerated testing paradigms for long-term implants.
CellGPS: Whole-body tracking of single cells by positron emission tomography
Authors: Jung Kyung Oh , Kim Tae Jin , Yu Jung Ho , Rhee Siyeon , Zhao Wei , Ha Byunghang , Red-Horse Kristy , Gambhir Sanjiv Sam , Pratx Guillem 
Published: August 2019

AbstractIn vivo molecular imaging tools are critically important for determining the role played by cell trafficking in biological processes and cellular therapies. However, existing tools measure average cell behavior and not the kinetics and migration routes of individual cells inside the body. Furthermore, efflux and non-specific accumulation of contrast agents are confounding factors, leading to inaccurate estimation of cell distribution in vivo. In view of these challenges, we report the development of a “cellular GPS” capable of tracking single cells inside living subjects with exquisite sensitivity. We use mesoporous silica nanoparticles (MSN) to concentrate 68Ga radioisotope into live cells and inject these cells into live mice. From the pattern of annihilation photons detected by positron emission tomography (PET), we infer, in real time, the position of individual cells with respect to anatomical landmarks derived from X-ray computed tomography (CT). To demonstrate this technique, a single human breast cancer cell was tracked in a mouse model of experimental metastasis. The cell arrested in the lungs 2-3 seconds after tail-vein injection. Its average velocity was estimated at around 50 mm/s, consistent with blood flow rate. Other cells were tracked after injection through other routes, but no motion was detected within 10 min of acquisition. Single-cell tracking could be applied to determine the kinetics of cell trafficking and arrest during the earliest phase of the metastatic cascade, the trafficking of immune cells during cancer immunotherapy, or the distribution of cells after transplantation in regenerative medicine.
Demonstrating and disrupting well-learned habits
Authors: Ceceli Ahmet O. , Myers Catherine E. , Tricomi Elizabeth 
Published: August 2019

AbstractResearchers have exerted tremendous efforts to empirically study how habits form and dominate at the expense of deliberation, yet we know very little about breaking these rigid habits to restore goal-directed control. In a three-experiment study, we first illustrate a novel approach of studying well-learned habits, in order to effectively demonstrate habit disruption. In Experiment 1, we use a Go/NoGo task with familiar color-response associations to demonstrate outcome-insensitivity when compared to novel, more flexible associations. Specifically, subjects perform more accurately when the required mapping is the familiar association of green–Go/red–NoGo than when it is red–Go/green–NoGo, confirming outcome-insensitive, habitual control. As a control condition, subjects show equivalent performance with unfamiliar color-response mappings (using the colors blue and purple mapped to Go and NoGo responses). Next, in Experiments 2 and 3, we test a motivation-based feedback manipulation in varying magnitudes (i.e., performance feedback with and without monetary incentives) to break the well-established habits elicited by our familiar stimuli. We find that although performance feedback prior to the contingency reversal test is insufficient to disrupt outcome-insensitivity in Experiment 2, a combination of performance feedback and monetary incentive is able to restore goal-directed control in Experiment 3, effectively breaking the habits. As the first successful demonstration of well-learned habit disruption in the laboratory, these findings provide new insights into how we execute and modify habits, while fostering new and translational research avenues that may be applicable to treating habit-based pathologies.
The efficiency for recombineering is dependent on the source of the phage recombinase function unit
Authors: Chang Yizhao , Wang Qian , Su Tianyuan , Qi Qingsheng 
Published: August 2019

AbstractPhage recombinase function units (PRFUs) such as lambda-Red or Rac RecET have been proven to be powerful genetic tools in the recombineering ofEscherichia coli. Studies have focused on developing such systems in other bacteria as it is believed that these PRFUs have limited efficiency in distant species. However, how the species evolution distance relates to the efficiency of recombineering remains unclear. Here, we present a thorough study of PRFUs to find features that might be related to the efficiency of PRFUs for recombineering. We first identified 59 unique sets of PRFUs in the genusCorynebacteriumand classified them based on their sequence as well as secondary structure similarities. Then both PRFUs from this genus and other bacteria were chosen for experiment based on sequential and secondary structure similarity as well as species distance. These PRFUs were compared for their ability in mediating recombineering with oligo or double-stranded DNA substrates inCorynebacterium glutamicum. We demonstrate that the source of the PRFU is more critical than species distance for the efficiency of recombineering. Our work will provide new ideas for efficient recombineering using PRFUs.ImportanceRecombineering using phage recombinase function units (PRFUs) such as lambda-Red or Rac RecET has gained success inEscherichia coli, while efforts applying these systems in other bacteria were limited by the efficiency. It is believed that the species distance may be a major reason for the low efficiency. In this study, however, we showed that it is the source of PRFU rather than the species distance that matters for the recombineering inCorynebacterium glutamicum. Besides, we also showed that the lower transformation efficiency in other bacteria compared to that ofE. colicould be a major reason for the low performance of heterogeneously expressed RecET. These findings will be helpful for the recombineering using PRFUs.
Neural circuits in the mouse retina support color vision in the upper visual field
Authors: Szatko Klaudia P. , Korympidou Maria M. , Ran Yanli , Berens Philipp , Dalkara Deniz , Schubert Timm , Euler Thomas , Franke Katrin 
Published: August 2019

ABSTRACTColor vision is essential to the survival of most animals. Its neural basis lies in the retina, where chromatic signals from different photoreceptor types sensitive to distinct wavelengths are locally compared by neural circuits. Mice, like most mammals, are generally dichromatic and have two cone photoreceptor types. However, in the ventral retina most cones display the same spectral preference, impairing spectral comparisons necessary for color vision. This conflicts with behavioral evidence showing that mice can discriminate colors only in the corresponding upper visual field. Here, we systematically investigated the neural circuits underlying mouse color vision across three processing stages of the retina by recording the output of cones, bipolar and ganglion cells using two-photon imaging. Surprisingly, we found that across all retinal layers most color-opponent cells were located in the ventral retina. This started at the level of the cone output, where color-opponency was mediated by horizontal cells and likely involving rod photoreceptors. Next, bipolar cells relayed the chromatic information to ganglion cells in the inner retina, where type-specific, non-linear center-surround interactions resulted in specific color-opponent output channels to the brain. This suggests that neural circuits in the mouse retina are specifically tuned to extract color information from the upper visual field, aiding robust detection of aerial predators and ensuring the animal’s survival.
Can natural selection favour indiscriminate spite?
Authors: Patel Matishalin , West Stuart A. , Biernaskie Jay M. 
Published: August 2019

AbstractSpiteful behaviours occur when an actor harms its own fitness to inflict harm on the fitness of others. Several papers have predicted that spite can be favoured in sufficiently small populations, even when the harming behaviour is directed indiscriminately at others. However, it is not clear that truly spiteful behaviour could be favoured without the harm being directed at a subset of social partners with relatively low genetic similarity to the actor (kin discrimination). Using mathematical models, we show that: (1) the evolution of spite requires kin discrimination; (2) previous models suggesting indiscriminate spite involve scenarios where the actor gains a direct feedback benefit from harming others, and so the harming is selfish rather than spiteful; (3) extreme selfishness can be favoured in small populations (and in some cases small groups) because this is where the feedback benefit of harming is greatest.
Cross frequency coupling in next generation inhibitory neural mass models
Authors: Ceni Andrea , Olmi Simona , Torcini Alessandro , Angulo-Garcia David 
Published: August 2019

Coupling among neural rhythms is one of the most important mechanisms at the basis of cognitive processes in the brain. In this study we consider a neural mass model, rigorously obtained from the microscopic dynamics of an inhibitory spiking network with exponential synapses, able to autonomously generate collective oscillations (COs). These oscillations emerge via a super-critical Hopf bifurcation, and their frequencies are controlled by the synaptic time scale, the synaptic coupling and the excitability of the neural population. Furthermore, we show that two inhibitory populations in a master-slave configuration with different synaptic time scales can display various collective dynamical regimes: namely, damped oscillations towards a stable focus, periodic and quasi-periodic oscillations, and chaos. Finally, when bidirectionally coupled the two inhibitory populations can exhibit different types of θ-γ cross-frequency couplings (CFCs): namely, phase-phase and phase-amplitude CFC. The coupling between θ and γ COs is enhanced in presence of a external θ forcing, reminiscent of the type of modulation induced in Hippocampal and Cortex circuits via optogenetic drive.In healthy conditions, the brain’s activity reveals a series of intermingled oscillations, generated by large ensembles of neurons, which provide a functional substrate for information processing. How single neuron properties influence neuronal population dynamics is an unsolved question, whose solution could help in the understanding of the emergent collective behaviors arising during cognitive processes. Here we consider a neural mass model, which reproduces exactly the macroscopic activity of a network of spiking neurons. This mean-field model is employed to shade some light on an important and ubiquitous neural mechanism underlying information processing in the brain: the θ-γ cross-frequency coupling. In particular, we will explore in detail the conditions under which two coupled inhibitory neural populations can generate these functionally relevant coupled rhythms.
An impressive capacity for cold tolerance plasticity protects against ionoregulatory collapse in the disease vector,Aedes aegypti
Authors: Jass Amanda , Yerushalmi Gil Y. , Davis Hannah E. , Donini Andrew , MacMillan Heath A. 
Published: August 2019

AbstractThe mosquitoAedes aegyptiis largely confined to tropical and subtropical regions but its range has recently been spreading to colder climates. As insect biogeography is closely tied to environmental temperature, understanding the limits ofAe. aegyptithermal tolerance and their capacity for phenotypic plasticity is important in predicting the spread of this species.In this study we report on the chill coma onset and recovery, as well as low temperature survival phenotypes of larvae and adults ofAedes aegyptithat developed or were acclimated to 15°C (cold) or 25°C (warm).Developmental cold acclimation did not affect chill coma onset of larvae but substantially reduced chill coma onset temperatures in adults. Chill coma recovery time was affected by both temperature and the duration of exposure, and developmental and adult acclimation both strongly mitigated these effects and increased rates of survival following prolonged chilling.Female adults were far less likely to take a blood meal when cold acclimated and simply exposing females to blood (without feeding) attenuated some of the beneficial effects of cold acclimation on chill coma recovery time.Lastly, larvae suffered from hemolymph hyperkalemia when chilled, but development in the cold attenuated the imbalance, which suggests that acclimation can prevent cold-induced ionoregulatory collapse in this species.Our results demonstrate thatAedes aegyptilarvae and adults have the capacity to acclimate to cold temperatures and do so at least in part by better maintaining ion balance in the cold. This ability for cold acclimation may facilitate the spread of this species to higher latitudes, particularly in an era of climate change.
A Latent Variable Model for Evaluation of Disparate Ratings of Stem Cell Colonies by Two Experts
Authors: Halter Michael , Lund Steven , Peskin Adele , Li-Baboud Ya-Shian , Bajcsy Peter , Aulov Oleg , Hoeppner Daniel J. , Chenoweth Joshua G. , Kim Suel-Kee , McKay Ronald D. , Plant Anne L. 
Published: August 2019

ABSTRACTThe visual inspection of pluripotent stem cell colonies by microscopy is widely used as a primary method to assess the quality of the preparations and degree of pluripotency. The lack of ground truth and the possible inconsistency of evaluations from multiple experts within and between stem cell laboratories are sources of uncertainty about the state of the cells, the reproducibility of preparations, and the efficiency of expansion protocols. To examine how to evaluate the level of confidence one has in disparate rating from experts, we explored a statistical method for assessing the differences in ratings of pluripotent stem cells by two different experts. Two experts rated phase contrast microscope images of human embryonic stem cell (hESC) colonies on a scale of 1 (poor) to 5 (maximum pluripotency character) but agreed with one another only 48% of the time. To assess whether experts used similar criteria to rate colonies, we developed custom image feature algorithms based on the stated visual criteria provided by the experts for selection of colonies. These features, plus others, were then used to develop pluripotency scoring algorithms trained to reflect ratings of both experts. We treated expert ratings as inexact indicators of a continuous pluripotency score and considered the inconsistency between expert ratings in developing our models. The model suggests that the two experts use somewhat different scales for discriminating between colony quality. Covariance analysis indicated that both experts use features that are not included in the model. Two image features, colony perimeter and a feature based on texture, were the most important for both experts for predicting the ratings. Interestingly, colony perimeter was not one of the expert-provided criteria for rating colonies, showing that this modeling approach allowed identification of features that the experts were not aware they were using. A linear model based on both experts identified each expert’s top-rated colonies as well as, or better than, the ratings of the other expert, as indicated by receiver operator characteristic curve analysis. By providing an understanding of the differences and similarities in disparate sets of expert ratings, this analysis helps to establish confidence in the ratings and the criteria for ratings, even when the experts disagree.
Evolution of resistance in vitro reveals a novel mechanism of artemisinin activity in Toxoplasma gondii
Authors: Rozenberg Alex , Luth Madeline R. , Winzeler Elizabeth A. , Behnke Michael , Sibley L. David 
Published: August 2019

AbstractArtemisinins are effective against a variety of parasites and provide the first line of treatment for malaria. Laboratory studies have identified several mechanisms for artemisinin resistance in Plasmodium falciparum, including mutations in Kelch13 that are associated with delayed clearance in some clinical isolates, although other mechanisms are likely involved. To explore other potential mechanisms of resistance in parasites, we took advantage of the genetic tractability of T. gondii, a related apicomplexan parasite that shows moderate sensitivity to artemisinin. Resistant populations of T. gondii were selected by culture in increasing drug concentrations and whole genome sequencing identified several non-conservative point mutations that emerged in the population and were fixed over time. Genome editing using CRISPR/Cas9 was used to introduce point mutations conferring amino acids changes in a serine protease homologous to DegP and a serine/threonine protein kinase of unknown function. Single and double mutations conferred a competitive advantage over wild type parasites in the presence of drug, despite not changing EC50 values. Additionally, the evolved resistant lines showed dramatic amplification of the mitochondrial genome, including genes encoding cytochrome b and cytochrome oxidase I. Consistent with prior studies in yeast and mammalian tumor cells that implicate the mitochondrion as a target of artemisinins, treatment of wild type parasites with artemisinin decreased mitochondrial membrane potential, and resistant parasites showed altered morphology and decreased membrane potential. These findings extend the repertoire of mutations associated with artemisinin resistance and suggest that the mitochondrion may be an important target of inhibition in T. gondii.SignificanceArtemisinins provide important therapeutic agents for treatment of malaria and have potential for use in other infections and in cancer. Their use is threatened by the potential for resistance development, so understanding their mechanism of action and identifying genetic changes that alter sensitivity are important for improving clinical outcomes. Our findings suggest that mutations in novel targets can contribute to the emergence of parasites with increased tolerance to artemisinin treatment and that such mutations can confer a fitness advantage even in the absence of a notable shift in EC50. Our findings also support the idea that inhibition of mitochondrial function may be an important target in T. gondii, as previously suggested by studies in yeast and human cancer cells.
Phylogenomics investigation of sparids (Teleostei: Spariformes) using high-quality proteomes highlights the importance of taxon sampling
Authors: Natsidis P , Tsakogiannis A , Pavlidis P , Tsigenopoulos CS , Manousaki T 
Published: August 2019

ABSTRACTSparidae (Teleostei: Spariformes) are a family of fish constituted by approximately 150 species with high popularity and commercial value, such as porgies and seabreams. Although the phylogeny of this family has been investigated multiple times, its position among other teleost groups remains ambiguous. Most studies have used a single or few genes to decipher the phylogenetic relationships of sparids. Here, we conducted a phylogenomic attempt to resolve the position of the family using five recently available Sparidae gene-sets and 26 available fish proteomes from species with a sequenced genome, to ensure higher quality of the predicted genes. A thorough phylogenomic analysis suggested that Tetraodontiformes (puffer fish, sunfish) are the closest relatives to sparids than all other groups used, a finding that contradicts our previous phylogenomic analysis that proposed the yellow croaker and the european seabass as closest taxa of sparids. By analytically comparing the methodologies applied in both cases, we show that this discordance is not due to different orthology assignment algorithms; on the contrary, we prove that it is caused by the increased taxon sampling of the present study, outlining the great importance of this aspect in phylogenomic analyses in general.