bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional connectivity signatures of NMDAR dysfunction in schizophrenia—integrating findings from imaging genetics and pharmaco-fMRI
Authors: Gaebler Arnim J. , Fakour Nilüfer , Stöhr Felix , Zweerings Jana , Taebi Arezoo , Suslova Mariia , Dukart Juergen , Hipp Joerg F. , Adhikari Bhim M. , Kochunov Peter , Muthukumaraswamy Suresh D. , Forsyth Anna , Eggermann Thomas , Kraft Florian , Kurth Ingo , Paulzen Michael , Gründer Gerhard , Schneider Frank , Mathiak Klaus 
Published: February 2023

AbstractBoth, pharmacological and genome-wide association studies suggest N-methyl-D-aspartate receptor (NMDAR) dysfunction and excitatory/inhibitory (E/I)-imbalance as a major pathophysiological mechanism of schizophrenia. The identification of shared fMRI brain signatures of genetically and pharmacologically induced NMDAR dysfunction may help to define biomarkers for patient stratification. NMDAR-related genetic and pharmacological effects on functional connectivity were investigated by integrating three different datasets: (A) resting state fMRI data from 146 patients with schizophrenia genotyped for the disease-associated genetic variant rs7191183 of GRIN2A (encoding the NMDAR 2 A subunit) as well as 142 healthy controls. (B) Pharmacological effects of the NMDAR antagonist ketamine and the GABA-A receptor agonist midazolam were obtained from a double-blind, crossover pharmaco-fMRI study in 28 healthy participants. (C) Regional gene expression profiles were estimated using a postmortem whole-brain microarray dataset from six healthy donors. A strong resemblance was observed between the effect of the genetic variant in schizophrenia and the ketamine versus midazolam contrast of connectivity suggestive for an associated E/I-imbalance. This similarity became more pronounced for regions with high density of NMDARs, glutamatergic neurons, and parvalbumin-positive interneurons. From a functional perspective, increased connectivity emerged between striato-pallido-thalamic regions and cortical regions of the auditory-sensory-motor network, while decreased connectivity was observed between auditory (superior temporal gyrus) and visual processing regions (lateral occipital cortex, fusiform gyrus, cuneus). Importantly, these imaging phenotypes were associated with the genetic variant, the differential effect of ketamine versus midazolam and schizophrenia (as compared to healthy controls). Moreover, the genetic variant was associated with language-related negative symptomatology which correlated with disturbed connectivity between the left posterior superior temporal gyrus and the superior lateral occipital cortex. Shared genetic and pharmacological functional connectivity profiles were suggestive of E/I-imbalance and associated with schizophrenia. The identified brain signatures may help to stratify patients with a common molecular disease pathway providing a basis for personalized psychiatry.
Association of the delayed changes in glutamate levels and functional connectivity with the immediate network effects of S-ketamine
Authors: Danyeli Lena Vera , Sen Zümrüt Duygu , Colic Lejla , Kurzweil Lisa , Gensberger-Reigl Sabrina , Macharadze Tamar , Götting Florian , Refisch Alexander , Liebe Thomas , Chand Tara , Kretzschmar Moritz , Wagner Gerd , Opel Nils , Jollant Fabrice , Speck Oliver , Munk Matthias H. J. , Li Meng , Walter Martin 
Published: February 2023

AbstractKetamine shows rapid antidepressant effects peaking 24 h after administration. The antidepressant effects may occur through changes in glutamatergic metabolite levels and resting-state functional connectivity (rsFC) within the default mode network (DMN). A multistage drug effect of ketamine has been suggested, inducing acute effects on dysfunctional network configuration and delayed effects on homeostatic synaptic plasticity. Whether the DMN-centered delayed antidepressant-related changes are associated with the immediate changes remains unknown. Thirty-five healthy male participants (25.1 ± 4.2 years) underwent 7 T magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (rsfMRI) before, during, and 24 h after a single S-ketamine or placebo infusion. Changes in glutamatergic measures and rsFC in the DMN node pregenual anterior cingulate cortex (pgACC) were examined. A delayed rsFC decrease of the pgACC to inferior parietal lobe (family-wise error corrected p (pFWEc) = 0.018) and dorsolateral prefrontal cortex (PFC; pFWEc = 0.002) was detected that was preceded by an immediate rsFC increase of the pgACC to medial PFC (pFWEc < 0.001) and dorsomedial PFC (pFWEc = 0.005). Additionally, the immediate rsFC reconfigurations correlated with the delayed pgACC glutamate (Glu) level increase (p = 0.024) after 24 h at trend level (p = 0.067). Baseline measures of rsFC and MRS were furthermore associated with the magnitude of the respective delayed changes (p’s < 0.05). In contrast, the delayed changes were not associated with acute psychotomimetic side effects or plasma concentrations of ketamine and its metabolites. This multimodal study suggests an association between immediate S-ketamine-induced network effects and delayed brain changes at a time point relevant in its clinical context.
Universal non-monotonic drainage in large bare viscous bubbles
Authors: Bartlett Casey , Oratis Alexandros T. , Santin Matthieu , Bird James C. 
Published: February 2023

AbstractBubbles will rest at the surface of a liquid bath until their spherical cap drains sufficiently to spontaneously rupture. For large film caps, the memory of initial conditions is believed to be erased due to a visco-gravitational flow, whose velocity increases from the top of the bubble to its base. Consequently, the film thickness has been calculated to be relatively uniform as it thins, regardless of whether the drainage is regulated by shear or elongation. Here, we demonstrate that for large bare bubbles, the film thickness is highly nonuniform throughout drainage, spanning orders of magnitude from top to base. We link the film thickness profile to a universal non-monotonic drainage flow that depends on the bubble thinning rate. These results highlight an unexpected coupling between drainage velocity and bubble thickness profiles and provide critical insight needed to understand the retraction and breakup dynamics of these bubbles upon rupture.
Genomics and biochemical analyses reveal a metabolon key to β-L-ODAP biosynthesis in Lathyrus sativus
Authors: Edwards Anne , Njaci Isaac , Sarkar Abhimanyu , Jiang Zhouqian , Kaithakottil Gemy George , Moore Christopher , Cheema Jitender , Stevenson Clare E. M. , Rejzek Martin , Novák Petr , Vigouroux Marielle , Vickers Martin , Wouters Roland H. M. , Paajanen Pirita , Steuernagel Burkhard , Moore Jonathan D. , Higgins Janet , Swarbreck David , Martens Stefan , Kim Colin Y. , Weng Jing-Ke , Mundree Sagadevan , Kilian Benjamin , Kumar Shiv , Loose Matt , Yant Levi , Macas Jiří , Wang Trevor L. , Martin Cathie , Emmrich Peter M. F. 
Published: February 2023

AbstractGrass pea (Lathyrus sativus L.) is a rich source of protein cultivated as an insurance crop in Ethiopia, Eritrea, India, Bangladesh, and Nepal. Its resilience to both drought and flooding makes it a promising crop for ensuring food security in a changing climate. The lack of genetic resources and the crop’s association with the disease neurolathyrism have limited the cultivation of grass pea. Here, we present an annotated, long read-based assembly of the 6.5 Gbp L. sativus genome. Using this genome sequence, we have elucidated the biosynthetic pathway leading to the formation of the neurotoxin, β-L-oxalyl-2,3-diaminopropionic acid (β-L-ODAP). The final reaction of the pathway depends on an interaction between L. sativus acyl-activating enzyme 3 (LsAAE3) and a BAHD-acyltransferase (LsBOS) that form a metabolon activated by CoA to produce β-L-ODAP. This provides valuable insight into the best approaches for developing varieties which produce substantially less toxin.
Oxidized mitochondrial DNA induces gasdermin D oligomerization in systemic lupus erythematosus
Authors: Miao Naijun , Wang Zhuning , Wang Qinlan , Xie Hongyan , Yang Ninghao , Wang Yanzhe , Wang Jin , Kang Haixia , Bai Wenjuan , Wang Yuanyuan , He Rui , Yan Kepeng , Wang Yang , Hu Qiongyi , Liu Zhaoyuan , Li Fubin , Wang Feng , Ginhoux Florent , Zhang Xiaoling , Yin Jianyong , Lu Limin , Wang Jing 
Published: February 2023

AbstractAlthough extracellular DNA is known to form immune complexes (ICs) with autoantibodies in systemic lupus erythematosus (SLE), the mechanisms leading to the release of DNA from cells remain poorly characterized. Here, we show that the pore-forming protein, gasdermin D (GSDMD), is required for nuclear DNA and mitochondrial DNA (mtDNA) release from neutrophils and lytic cell death following ex vivo stimulation with serum from patients with SLE and IFN-γ. Mechanistically, the activation of FcγR downregulated Serpinb1 following ex vivo stimulation with serum from patients with SLE, leading to spontaneous activation of both caspase-1/caspase-11 and cleavage of GSDMD into GSDMD-N. Furthermore, mtDNA oxidization promoted GSDMD-N oligomerization and cell death. In addition, GSDMD, but not peptidyl arginine deiminase 4 is necessary for extracellular mtDNA release from low-density granulocytes from SLE patients or healthy human neutrophils following incubation with ICs. Using the pristane-induced lupus model, we show that disease severity is significantly reduced in mice with neutrophil-specific Gsdmd deficiency or following treatment with the GSDMD inhibitor, disulfiram. Altogether, our study highlights an important role for oxidized mtDNA in inducing GSDMD oligomerization and pore formation. These findings also suggest that GSDMD might represent a possible therapeutic target in SLE.
Long-term soil warming decreases microbial phosphorus utilization by increasing abiotic phosphorus sorption and phosphorus losses
Authors: Tian Ye , Shi Chupei , Malo Carolina Urbina , Kwatcho Kengdo Steve , Heinzle Jakob , Inselsbacher Erich , Ottner Franz , Borken Werner , Michel Kerstin , Schindlbacher Andreas , Wanek Wolfgang 
Published: February 2023

AbstractPhosphorus (P) is an essential and often limiting element that could play a crucial role in terrestrial ecosystem responses to climate warming. However, it has yet remained unclear how different P cycling processes are affected by warming. Here we investigate the response of soil P pools and P cycling processes in a mountain forest after 14 years of soil warming (+4 °C). Long-term warming decreased soil total P pools, likely due to higher outputs of P from soils by increasing net plant P uptake and downward transportation of colloidal and particulate P. Warming increased the sorption strength to more recalcitrant soil P fractions (absorbed to iron oxyhydroxides and clays), thereby further reducing bioavailable P in soil solution. As a response, soil microbes enhanced the production of acid phosphatase, though this was not sufficient to avoid decreases of soil bioavailable P and microbial biomass P (and biotic phosphate immobilization). This study therefore highlights how long-term soil warming triggers changes in biotic and abiotic soil P pools and processes, which can potentially aggravate the P constraints of the trees and soil microbes and thereby negatively affect the C sequestration potential of these forests.
Visualizing orthogonal RNAs simultaneously in live mammalian cells by fluorescence lifetime imaging microscopy (FLIM)
Authors: Sarfraz Nadia , Moscoso Emilia , Oertel Therese , Lee Harrison J. , Ranjit Suman , Braselmann Esther 
Published: February 2023

AbstractVisualization of RNAs in live cells is critical to understand biology of RNA dynamics and function in the complex cellular environment. Detection of RNAs with a fluorescent marker frequently involves genetically fusing an RNA aptamer tag to the RNA of interest, which binds to small molecules that are added to live cells and have fluorescent properties. Engineering efforts aim to improve performance and add versatile features. Current efforts focus on adding multiplexing capabilities to tag and visualize multiple RNAs simultaneously in the same cell. Here, we present the fluorescence lifetime-based platform Riboglow-FLIM. Our system requires a smaller tag and has superior cell contrast when compared with intensity-based detection. Because our RNA tags are derived from a large bacterial riboswitch sequence family, the riboswitch variants add versatility for using multiple tags simultaneously. Indeed, we demonstrate visualization of two RNAs simultaneously with orthogonal lifetime-based tags.
A wheat kinase and immune receptor form host-specificity barriers against the blast fungus
Authors: Arora Sanu , Steed Andrew , Goddard Rachel , Gaurav Kumar , O’Hara Tom , Schoen Adam , Rawat Nidhi , Elkot Ahmed F. , Korolev Andrey V. , Chinoy Catherine , Nicholson Martha H. , Asuke Soichiro , Antoniou-Kourounioti Rea , Steuernagel Burkhard , Yu Guotai , Awal Rajani , Forner-Martínez Macarena , Wingen Luzie , Baggs Erin , Clarke Jonathan , Saunders Diane G. O. , Krasileva Ksenia V. , Tosa Yukio , Jones Jonathan D. G. , Tiwari Vijay K. , Wulff Brande B. H. , Nicholson Paul 
Published: February 2023

AbstractSince emerging in Brazil in 1985, wheat blast has spread throughout South America and recently appeared in Bangladesh and Zambia. Here we show that two wheat resistance genes, Rwt3 and Rwt4, acting as host-specificity barriers against non-Triticum blast pathotypes encode a nucleotide-binding leucine-rich repeat immune receptor and a tandem kinase, respectively. Molecular isolation of these genes will enable study of the molecular interaction between pathogen effector and host resistance genes.
The evolution of pit morphology and growth kinetics in aluminum during atmospheric corrosion
Authors: Noell Philip J. , Karasz Erin , Schindelholz Eric J. , Polonsky Andrew T. , Campbell Ian , Katona Ryan M. , Melia Michael A. 
Published: February 2023

AbstractAssessing the lifetimes of alloys in humid, corrosive environments requires growth kinetic information regarding individual instances of damage, e.g. pit growth rates. Corrosion rates measured at the continuum scale using mass change convolute the rate of pit nucleation and growth, providing limited information on local kinetics. The current study used in-situ X-ray computed tomography to measure growth rates of individual pits in aluminum over 100 h of exposure in a humid, chloride environment. While pits grew at relatively constant rates over the first hours after nucleation, significant growth-rate nonlinearities subsequently occurred. These were linked to both droplet spreading, which altered the cathode size, and changes in the mode of pit growth. Pit morphology appeared to influence the dominant growth mode and the duration of pit growth. Post-mortem serial sectioning revealed pits preferentially attacked grain-boundary triple junctions and dislocation boundaries.
A subwavelength atomic array switched by a single Rydberg atom
Authors: Srakaew Kritsana , Weckesser Pascal , Hollerith Simon , Wei David , Adler Daniel , Bloch Immanuel , Zeiher Johannes 
Published: February 2023

AbstractEnhancing light–matter coupling at the level of single quanta is essential for numerous applications in quantum science. The cooperative optical response of subwavelength atomic arrays has been found to open new pathways for such strong light–matter couplings, while simultaneously offering access to multiple spatial modes of the light field. Efficient single-mode free-space coupling to such arrays has been reported, but spatial control over the modes of outgoing light fields has remained elusive. Here, we demonstrate such spatial control over the optical response of an atomically thin mirror formed by a subwavelength array of atoms in free space using a single controlled ancilla atom excited to a Rydberg state. The switching behaviour is controlled by the admixture of a small Rydberg fraction to the atomic mirror, and consequently strong dipolar Rydberg interactions with the ancilla. Driving Rabi oscillations on the ancilla atom, we demonstrate coherent control of the transmission and reflection of the array. These results represent a step towards the realization of quantum coherent metasurfaces, the demonstration of controlled atom–photon entanglement and deterministic engineering of quantum states of light.
Unravelling microalgal-bacterial interactions in aquatic ecosystems through 16S rRNA gene-based co-occurrence networks
Authors: Pushpakumara B. L. D. Uthpala , Tandon Kshitij , Willis Anusuya , Verbruggen Heroen 
Published: February 2023

AbstractInteractions between microalgae and bacteria can directly influence the global biogeochemical cycles but the majority of such interactions remain unknown. 16S rRNA gene-based co-occurrence networks have potential to help identify microalgal-bacterial interactions. Here, we used data from 10 Earth microbiome projects to identify potential microalgal-bacterial associations in aquatic ecosystems. A high degree of clustering was observed in microalgal-bacterial modules, indicating densely connected neighbourhoods. Proteobacteria and Bacteroidetes predominantly co-occurred with microalgae and represented hubs of most modules. Our results also indicated that species-specificity may be a global characteristic of microalgal associated microbiomes. Several previously known associations were recovered from our network modules, validating that biologically meaningful results can be inferred using this approach. A range of previously unknown associations were recognised such as co-occurrences of Bacillariophyta with uncultured Planctomycetes OM190 and Deltaproteobacteria order NB1-j. Planctomycetes and Verrucomicrobia were identified as key associates of microalgae due to their frequent co-occurrences with several microalgal taxa. Despite no clear taxonomic pattern, bacterial associates appeared functionally similar across different environments. To summarise, we demonstrated the potential of 16S rRNA gene-based co-occurrence networks as a hypothesis-generating framework to guide more focused research on microalgal-bacterial associations.
1′-O-methyl-averantin isolated from the endolichenic fungus Jackrogersella sp. EL001672 suppresses colorectal cancer stemness via sonic Hedgehog and Notch signaling
Authors: Varlı Mücahit , Lee Eun-Young , Yang Yi , Zhou Rui , Taş İsa , Pulat Sultan , Gamage Chathurika D. B. , Park So-Yeon , Hur Jae-Seoun , Nam Sang-Jip , Kim Hangun 
Published: February 2023

AbstractEndolichenic fungi are host organisms that live on lichens and produce a wide variety of secondary metabolites. Colorectal cancer stem cells are capable of self-renewal and differentiation into cancer cells, which makes cancers difficult to eradicate. New alternative therapeutics are needed to inhibit the growth of tumor stem cells. This study examined the ability of an extract of Jackrogersella sp. EL001672 (derived from the lichen Cetraria sp.) and the isolated compound 1′-O-methyl-averantin to inhibit development of cancer stemness. The endolichenic fungus Jackrogersella sp. EL001672 (KACC 83021BP), derived from Cetraria sp., was grown in culture medium. The culture broth was extracted with acetone to obtain a crude extract. Column chromatography and reverse-phase HPLC were used to isolate an active compound. The anticancer activity of the extract and the isolated compound was evaluated by qRT-PCR and western blotting, and in cell viability, spheroid formation, and reporter assays. The acetone extract of EL001672 did not affect cell viability. However, 1′-O-methyl-averantin showed cytotoxic effects against cancer cell lines at 50 μg/mL and 25 μg/mL. Both the crude extract and 1′-O-methyl-averantin suppressed spheroid formation in CRC cell lines, and downregulated expression of stemness markers ALDH1, CD44, CD133, Lgr-5, Msi-1, and EphB1. To further characterize the mechanism underlying anti-stemness activity, we examined sonic Hedgehog and Notch signaling. The results showed that the crude extract and the 1′-O-methyl-averantin inhibited Gli1, Gli2, SMO, Bmi-1, Notch-1, Hes-1, and the CSL complex. Consequently, an acetone extract and 1′-O-methyl-averantin isolated from EL001672 suppresses colorectal cancer stemness by regulating the sonic Hedgehog and Notch signaling pathways.
Optimized protocol for MALDI MSI of N-glycans using an on-tissue digestion in fresh frozen tissue sections
Authors: Grgic Andrej , Krestensen Kasper K. , Heeren Ron M. A. 
Published: February 2023

AbstractGlycans play an important role in biology with multiple cellular functions ranging from cell signaling, mobility and growth to protein folding and localization. The N-glycosylation state within a tissue has been found to vary greatly between healthy and diseased patients and has proven to have an important clinical diagnostic value. Matrix assisted laser-desorption ionization (MALDI) mass spectrometry imaging (MSI) allows for untargeted analysis of biomolecules, including N-glycans, on a tissue section and provides a spatial context of the analyte. Until now, N-glycans have been predominantly analyzed using MALDI MSI on formalin-fixed paraffin embedded (FFPE) tissue sections, however this greatly reduces the clinical applicability, as the FFPE embedding process alters the biological environment of the tissue. Here we developed a protocol that allows for MALDI MSI of N-glycans from fresh frozen tissue that matches the current standard of FFPE analysis. By optimizing several steps in the sample preparation, we see orders of magnitude increase in signal intensity. Furthermore, this method limits delocalization of released N-glycans, thus improving the effective spatial resolution of the label-free molecular images. This protocol provides a novel perspective towards clinical application of MALDI MSI and capitalizes on the diagnostic value of N-glycan analysis.
Climate-driven convergent evolution in riparian ecosystems on sky islands
Authors: Love S. J. , Schweitzer J. A. , Bailey J. K. 
Published: February 2023

AbstractClimate-induced evolution will determine population persistence in a changing world. However, finding natural systems in which to study these responses has been a barrier to estimating the impact of global change on a broad scale. We propose that isolated sky islands (SI) and adjacent mountain chains (MC) are natural laboratories for studying long-term and contemporary climatic pressures on natural populations. We used greenhouse common garden trees to test whether populations on SI exposed to hot and dry climates since the end of the Pleistocene have phenotypically diverged from populations on MC, and if SI populations have converged in these traits. We show: (1) populations of Populus angustifolia from SI have diverged from MC, and converged across SI, in reproductive and productivity traits, (2) these traits (cloning and aboveground biomass, respectively) are significantly correlated, suggesting a genetic linkage between them, and (3) the trait variation is driven by both natural selection and genetic drift. These shifts represent potentially beneficial phenotypes for population persistence in a changing world. These results suggest that the SI–MC comparison is a natural laboratory, as well as a predictive framework, for studying long-term responses to climate change across the globe.