bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Scale Spatio-Chemical Control of the Activating-Inhibitory Signal Integration in NK Cells
Authors: Toledo Esti , Le Saux Guillaume , Li Long , Rosenberg Maor , Keidar Yossi , Bhingardive Viraj , Edri Avishay , Hadad Uzi , Di Primo Carmelo , Buffeteau Thierry , Smith Ana-Sunčana , Porgador Angel , Schvartzman Mark 
Published: March 2020

AbstractThe role of the spatial juxtaposition between activating and inhibitory receptors in cytotoxic lymphocytes has been strongly debated in the context of the inhibition of immune signaling. The challenge in addressing this problem was so far a lack of experimental tools which can simultaneously manipulate different signaling molecules. Here, we circumvent this challenge by introducing a nanoengineered multifunctional cell niche, in which activating and inhibitory ligands are positioned with molecular-scale variability and control, and applied it to elucidate the role of the spatial juxtaposition between ligands for NKG2D and KIR2DL1 – activating and inhibitory receptors in Natural Killer (NK) cells – in KIR2DL1-mediated inhibition of NKG2D signaling. We realized the niche by a nanopatterning of nanodots of different metals with molecular scale registry in one lithographic step, followed by a novel ternary functionalization of the fabricated bi-metallic pattern and its background to with three distinct biochemical moieties. We found, that within the probed range, the 40 nm gap between the activating and inhibitory ligands provided an optimal inhibition condition. Supported by theoretical modeling and simulations we interpret these findings as a consequence of the size and conformational flexibility of the ligands in their spatial interaction. Our findings provide an important insight onto the spatial mechanism of the inhibitory immune checkpoints, whose understanding is both fundamentally important, and essential for the rational design of future immunotherapies. Furthermore, our approach is highly versatile and paves the way to numerous complex molecular platforms aimed at revealing molecular mechanisms through which receptors integrate their signals.
Temporal environmental variation imposes differential selection on genomic and ecological traits of virtual plant communities
Authors: Leidinger Ludwig , Cabral Juliano Sarmento 
Published: March 2020

AbstractThe reaction of species to changing conditions determines how community composition will change functionally — not only by (temporal) species turnover, but also by trait shifts within species. For the latter, selection from standing variation has been suggested to be more efficient than acquiring new mutations. Yet, studies on community trait composition and trait selection largely focus on phenotypic variation in ecological traits, whereas the underlying genomic traits remain relatively understudied despite evidence of their role to standing variation. Using a genome-explicit, niche- and individual-based model, we address the potential interactions between genomic and ecological traits shaping communities under an environmental selective forcing, namely temporal variation. In this model, all ecological traits are explicitly coded by the genome. For our experiments, we initialized 90 replicate communities, each with ca. 350 initial species, characterized by random genomic and ecological trait combinations, on a 2D spatially-explicit landscape with two orthogonal gradients (temperature and resource use). We exposed each community to two contrasting scenarios: without (i.e. static environments) and with temporal variation. We then analyzed emerging compositions of both genomic and ecological traits at the community, population and genomic levels. Communities in variable environments were species poorer than in static environments, populations more abundant and genomes had a higher numbers of genes. The surviving genomes (i.e. those selected by variable environments) coded for enhanced environmental tolerance and smaller biomass, which resulted in faster life cycles and thus also in increased potential for evolutionary rescue. Even under the constant environmental filtering presented by temporal environmental variation, larger, more linked genomes allowed selection of increased variation in dispersal abilities. Our results provide clues to how sexually-reproducing diploid plant communities might react to increased environmental variation and highlights the importance of genomic traits and their interaction with ecological traits for eco-evolutionary responses to changing climates.
Segment-Specific Optogenetic Stimulation inDrosophila melanogasterwith Linear Arrays of Organic Light-Emitting Diodes
Authors: Murawski Caroline , Pulver Stefan R. , Gather Malte C. 
Published: March 2020

AbstractOptogenetics allows light-driven, non-contact control of neural systems, but light delivery remains challenging, in particular when fine spatial control of light is required to achieve local specificity. Here, we employ organic light-emitting diodes (OLEDs) that are micropatterned into linear arrays to obtain precise optogenetic control inDrosophila melanogasterlarvae expressing the light-gated activator CsChrimson and the inhibitor GtACR2 within their peripheral sensory system. Our method allows confinement of light stimuli to within individual abdominal segments, which facilitates the study of larval behaviour in response to local sensory input. We show controlled triggering of specific crawling modes and find that targeted neurostimulation in abdominal segments switches the direction of crawling. More broadly, our work demonstrates how OLEDs can provide tailored patterns of light for photo-stimulation of neuronal networks, with future implications ranging from mapping neuronal connectivity in cultures to targeted photo-stimulation with pixelated OLED implantsin vivo.
Methylation Data Processing Protocol & Comparison of Blood and Cerebral Spinal Fluid Following Aneurysmal Subarachnoid Hemorrhage
Authors: Arockiaraj Annie I. , Liu Dongjing , Shaffer John R. , Koleck Theresa A. , Crago Elizabeth A. , Weeks Daniel E. , Conley Yvette P. 
Published: March 2020

AbstractOne challenge in conducting DNA methylation-based epigenome-wide association studies (EWAS) is the appropriate cleaning and quality-checking of the methylation values to minimize biases and experimental artifacts, while simultaneously retaining potential biological signals. These issues are compounded in studies that include multiple tissue types, and/or tissues for which reference data are unavailable to assist in adjusting for cell-type mixture, for example cerebral spinal fluid (CSF). For our study that evaluated blood and CSF taken from aneurysmal subarachnoid hemorrhage (aSAH) patients, we developed a protocol to clean and quality-check genome-wide methylation levels and compared the methylomic profiles of the two tissues to determine whether blood is a suitable surrogate for CSF. CSF samples were collected from 279 aSAH patients longitudinally during the first 14 days of hospitalization, and a subset of 88 of these patients also provided blood samples within the first two days. Quality control (QC) procedures included identification and exclusion of poor performing samples and low-quality probes, functional normalization, and correction for cell-type heterogeneity via surrogate variable analysis (SVA). Significant differences in rates of poor sample performance was observed between blood (1.1% failing QC) and CSF (9.12% failing QC; p = 0.003). Functional normalization increased the concordance of methylation values among technical replicates in both CSF and blood. Likewise, SVA improved the asymptotic behavior of the test of association in a simulated EWAS under the null hypothesis. To determine the suitability of blood as a surrogate for CSF, we calculated the correlation of adjusted methylation values between blood and CSF globally and by genomic regions. Overall, mean correlation (r < 0.26) was low, suggesting that blood is not a suitable surrogate for global methylation in CSF. However, differences in the magnitude of the correlation were observed by genomic region (CpG island, shore, shelf, open sea; p < 0.001 for all) and orientation with respect to nearby genes (3’ UTR, transcription start site, exon, body, 5’ UTR; p < 0.01 for all). In conclusion, the correlation analysis and QC pipelines indicated that DNA extracted from blood was not, overall, a suitable surrogate for DNA extracted from CSF in aSAH methylomic studies.
Tumor MHCII immunity requires in situ antigen presentation by cancer-associated fibroblasts
Authors: Kerdidani Dimitra , Aerakis Emmanouil , Verrou Kleio-Maria , Stamoulis Petros , Goudevenou Katerina , Prados Alejandro , Tzaferis Christos , Vamvakaris Ioannis , Kaniaris Evangelos , Vachlas Konstantinos , Sepsas Evangelos , Potaris Konstantinos , Koutsopoulos Anastasios , Tsoumakidou Maria 
Published: March 2020

ABSTRACTA key unknown of the functional space in tumor immunity is whether physiologically relevant cancer antigen presentation occurs solely in draining lymph nodes versus tumors. Professional antigen presenting cells, i.e. the dendritic cells, are scarce and immature within tumors, greatly outnumbered by MHCII expressing non-hematopoietic cells, such as antigen-presenting cancer-associated fibroblasts (apCAFs). We hypothesized that after their exit from tumor-draining lymph nodes T cells depend on a second wave of antigen presentation provided in situ by structural cells. We show that dense apCAF regions in human lung tumors define hot immunological spots with increased numbers of CD4 T cells. The transcriptomic profile of human lung apCAFs aligned to that of pancreatic apCAFs across mice and humans and were both enriched for alveolar type II genes, suggesting an epithelial origin. Mechanistically, human apCAFs directly activated the TCRs of adjacent effector CD4 T cells and at the same time produced high levels of c1q, which acted on surface c1qbp on T cells to rescue them from apoptosis. Fibroblast-specific deletion of MHCII in mice impaired local MHCII immunity and accelerated tumor growth, while inducing c1qbp overexpression in adoptively transferred T cells expanded their numbers within tumors and reduced tumour burden. Collectively, our work shows that tumor T cell immunity post lymph node exit requires peripheral antigen presentation by a subset of CAFs and proposes a new conceptual framework upon which effective cancer immunotherapies can be built.
FSD1: a plastidial, nuclear and cytoplasmic enzyme relocalizing to the plasma membrane under salinity
Authors: Dvořák Petr , Krasylenko Yuliya , Ovečka Miroslav , Basheer Jasim , Zapletalová Veronika , Šamaj Jozef , Takáč Tomáš 
Published: March 2020

AbstractHere, we aimed to resolve the developmental expression and subcellular localization ofArabidopsisiron superoxide dismutase FSD1, which belongs to the family of superoxide dismutases (SODs), prominent enzymes decomposing superoxide anion and determining abiotic stress tolerance. We found thatfsd1knockout mutants exhibit reduced lateral root number and that this phenotype was complemented byproFSD1::GFP:FSD1andproFSD1::FSD1:GFPconstructs. Light sheet fluorescence microscopy revealed a temporary accumulation of FSD1-GFP at the site of endosperm rupture during seed germination. In emerged roots, FSD1-GFP showed the highest abundance in cells of the lateral root cap, columella, and endodermis/cortex initials. The largest subcellular pool of FSD1-GFP was localized in the plastid stroma, while it was also located in the nuclei and cytoplasm. FSD1 is crucial for seed germination and salt stress tolerance, which is tightly coupled with FSD1-GFP subcellular relocation to the plasma membrane. FSD1 is most likely involved in superoxide decomposition in the periplasm. This study suggests a new osmoprotective function of SODs in plants.
Vocal convergence in a multi-level primate society: insights into the evolution of vocal learning
Authors: Fischer Julia , Wegdell Franziska , Trede Franziska , Pesco Federica Dal , Hammerschmidt Kurt 
Published: March 2020

ABSTRACTThe extent to which nonhuman primate vocalizations are amenable to modification through experience is relevant for understanding the substrate from which human speech evolved. We examined the vocal behaviour of Guinea baboons,Papio papio, ranging in the Niokolo Koba National Park in Senegal. Guinea baboons live in a multi-level society, with units nested within parties nested within gangs. We investigated whether the acoustic structure of grunts of 27 male baboons of two gangs varied with party/gang membership and genetic relatedness. Males in this species are philopatric, resulting in increased male relatedness within gangs and parties. Grunts from members were more similar within than across social levels (N = 351 dyads for comparison within and between gangs, and N = 169 dyads within and between parties), but the effect sizes were small. Yet, acoustic similarity did not correlate with genetic relatedness, suggesting that higher amounts of social interactions rather than genetic relatedness promote the observed vocal convergence. We consider this convergence a result of sensory-motor integration and suggest this to be an implicit form of vocal learning shared with humans, in contrast to the goal-directed and intentional explicit form of vocal learning unique to human speech acquisition.
Evidence for a growth zone for deep subsurface microbial clades in near-surface anoxic sediments
Authors: Lloyd Karen G. , Bird Jordan T. , Buongiorno Joy , Deas Emily , Kevorkian Richard , Noordhoek Talor , Rosalsky Jacob , Roy Taylor 
Published: March 2020

AbstractGlobal marine sediments harbor a large and highly diverse microbial biosphere, but the mechanism by which this biosphere is established during sediment burial is largely unknown. During burial in marine sediments, concentrations of easily-metabolized organic compounds and total microbial cell abundance decrease steadily. However, it is unknown whether some microbial clades increase with depth, despite the overall trend of abundance decrease. We show total population increases in 38 microbial families over 3 cm of sediment depth in the upper 7.5 cm of White Oak River (WOR) estuary sediments. Clades that increased with depth were more often anaerobic, uncultured, or common in deep marine sediments relative to those that decreased. Minimum turnover times (which are minimumin situdoubling times of growth rates) were estimated to be 2-25 years by combining sedimentation rate with either quantitative PCR (qPCR) or the product of the Fraction Read Abundance of 16S rRNA genes and total Cell counts (FRAxC). Turnover times were within an order of magnitude of each other in two adjacent cores, as well as in two laboratory enrichments of Cape Lookout Bight (CLB), NC, sediments (average difference of 28 ± 19%). qPCR and FRAxC in WOR cores and FRAxC in CLB incubations produced similar turnover times for key deep subsurface uncultured cladesBathyarchaeota(8.7 ± 1.9 years) andThermoprofundales/MBG-D (4.1 ± 0.7 years). We conclude that common deep subsurface microbial clades experience a narrow zone of growth in shallow sediments, offering an opportunity for natural selection of traits for long-term subsistence after resuspension events.Significance statementThe current dogma is that the deeply-branching uncultured microbes that dominate global marine sediments do not actually increase in population size as they are buried in marine sediments – rather they exist in a sort of prolonged torpor for thousands of years. This is because no evidence has ever been found that these clades actually increase population sizes, or grow, as they are gradually buried. We discovered that they actually do increase population sizes during burial, but only in the upper few centimeters. This changes our dogma about marine sediments as a vast repository of non-growing microbes, to a vast repository of non-growing microbes with a thin and relatively rapid area of growth in the upper 10 centimeters.
Narrow oviposition preference of an insect herbivore risks survival under conditions of severe drought
Authors: Salgado Ana L. , DiLeo Michelle F. , Saastamoinen Marjo 
Published: March 2020

ABSTRACTUnderstanding species’ habitat preferences are crucial to predict organisms’ responses to the current climate crisis. In many insects, maternal habitat selection for oviposition essentially determines offspring performance. Whether changes in climatic conditions may pose future mismatches in oviposition preference and offspring performance when mothers continue to prefer microhabitats that now threaten offspring survival is an open question.To address this, we tested if oviposition preferences put offspring at risk in the Glanville fritillary butterfly (Melitaea cinxia) under drought stress. Mainly, we focus on identifying the microhabitat determinants for oviposition and the variation of conditions experienced by the sessile offspring, using field observations from 12 populations collected over 2015-2018. These data are combined with ten years of larval nest and precipitation data to understand within-population patterns of habitat selection. We tested whether the preferred microhabitats maximized the extended larval performance (i.e. overwinter survival).We found that females preferentially oviposited in microhabitats with higher host plant abundance and higher proportion of host plants with signs of drought stress. In most years, larval nests had higher survival in these drought-stressed microhabitats. However, in an extremely dry year, only two nests survived over the summer.Our results highlight that a failure to shift habitat preference under extreme climate conditions may have drastic consequences for the survival of natural populations under changing climatic conditions.
Visualization of the initial fixed nitrogen transport in nodulated soybean plant using [13N]N2tracer gas in real-time
Authors: Nguyen Hung V. P. , Thi Hue Tong 
Published: March 2020

AbstractThe observation of initial transport of fixed nitrogen in intact soybean plants in real-time was conducted by using the positron-emitting tracer imaging system (PETIS). Soybean root nodules were fed with [13N]N2for 10 minutes, and the radioactivity of [13N]N tracer was recorded for 60 minutes. The serial images of nitrogen fixation activity and translocation of fixed nitrogen in the soybean plant were reconstructed to estimate the fixed-N transport to the upper shoot. As a result, the signal of nitrogen radiotracer moving upward through the intact stem was successfully observed. This is the first report that the translocation of fixed-N is visualized in real-time in soybean plant by a moving image. The signal of nitrogen radiotracer appeared at the base stem at about 20 minutes after the feeding of tracer gas and it took 40 minutes to reach the upper stem. The velocity of fixed nitrogen translocation was estimated approximately at 1.63 cm min-1. The autoradiography taken after PETIS experiment showed a clear picture of transport of fixed13N in the whole plant that the fixed-N moved not only via xylem system but also via the phloem system to the shoot after transferring from xylem to phloem in the stem although it has been generally considered that the fixed-N in nodule is transported dominantly via xylem by transpiration stream toward mature leaves. This result also suggests that the initial transport of fixed-N was mainly into the stem and subsequently translocated to young leaves and buds via the phloem system. These new findings in the initial transport of fixed nitrogen of soybean by PETIS observation will become the basis for future study of fixed-N transport in the whole legume plants.
High-content image-based drug screen identifies a clinical compound against cell transmission of adenovirus
Authors: Georgi Fanny , Kuttler Fabien , Murer Luca , Andriasyan Vardan , Witte Robert , Yakimovich Artur , Turcatti Gerardo , Greber Urs F 
Published: March 2020

AbstractHuman adenoviruses (HAdVs) are fatal to immuno-suppressed people, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus entry to dissemination of progeny. We analysed 1,280 small molecular weight compounds of the Prestwick Chemical Library (PCL) for interference with HAdV-C2 infection in a quadruplicate, blinded format, and included robust image analyses, and hit filtering. We present the entire set of the screening data including all the images, image analyses and data processing pipelines. The data are made available at the Image Data Repository (IDR)1, accession number idr0081. Our screen identified Nelfinavir mesylate as an inhibitor of HAdV-C2 multi-round plaque formation, but not single round infection. Nelfinavir has been FDA-approved for anti-retroviral therapy in humans. Our results underscore the power of image-based full cycle infection assays in identifying viral inhibitors with clinical potential.
No room to roam: King Cobras reduce movement in agriculture
Authors: Marshall Benjamin Michael , Crane Matt , Silva Inês , Strine Colin Thomas , Jones Max Dolton , Hodges Cameron Wesley , Suwanwaree Pongthep , Artchawakom Taksin , Waengsothorn Surachit , Goode Matt 
Published: March 2020

AbstractStudying animal movement provides insights into how animals react to land-use changes, specifically how animals can change their behaviour in agricultural areas. Recent reviews show a tendency for species to reduce movements in response to increased human landscape modification, but the study of movement has not been extensively explored in reptiles. We examined movements of a large reptilian predator, the King Cobra (Ophiophagus hannah), in Northeast Thailand. We used a consistent regime of radio-telemetry tracking to document movements across protected forest and adjacent agricultural areas. We then adapted GPS-targeting analytic methods to examine the movement using metrics of site reuse and dynamic Brownian Bridge Movement Model derived motion variance. Examination of motion variance demonstrated that King Cobra movements increased in forested areas and tended to decrease in agricultural areas. Our Integrated Step-Selection Functions indicated that when moving in agricultural areas King Cobras restricted their movements, thereby remaining within vegetated semi-natural areas, often located along the banks of irrigation canals. Site reuse metrics of residency time and number of revisits remained unaffected by distance to landscape features. Neither motion variance nor reuse metrics were consistently affected by the presence of threatening landscape features (e.g. roads, human settlements); suggesting that King Cobras will remain in close proximity to threats, provided habitat patches are available. Although King Cobras displayed heterogeneity in their response to agricultural landscapes, the overall trend suggested a reduction in movements when faced with fragmented habitat patches embedded in an otherwise inhospitable land-use matrix. Reductions in movements are consistent with findings for mammals and forest specialist species.