bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycogen-fuelled metabolism supports rapid Mucosal Associated Invariant T cell responses
Authors: Cassidy Féaron C. , Kedia-Mehta Nidhi , Bergin Ronan , Woodcock Andrea , Berisha Ardena , Bradley Ben M. , Booth Eva , Ryan Odhran K. , Sinclair Linda V. , O’Shea Donal , Hogan Andrew E. 
Published: December 2022

AbstractMucosal Associated Invariant T (MAIT) cells are a subset of unconventional T cells, which recognise a limited repertoire of ligands presented by the MHC class I-like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties and rapid effector functions, MAIT cells are emerging as attractive candidates for cancer-immunotherapy. In the current study, we demonstrate that MAIT cells are potent anti-tumour cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 hours. However, the metabolic processes supporting rapid MAIT cell anti-tumour responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (<3 hours) cytokine production, as is oxidative phosphorylation. We show for the first time that MAIT cells have the machinery required to make and metabolize glycogen, and demonstrate that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. In summary, we show for the first time that glycogen-fuelled metabolism supports rapid MAIT cell effector functions (cytotoxicity and cytokine production) which may have implications in their use as an immunotherapeutic agent.
Systems Level Identification of a Matrisome-Associated Macrophage Polarization State in Multi-Organ Fibrosis
Authors: Huang Kevin Y. , Mishra Kunal , Park Harry , Yi Xie , Ouyang John F. , Petretto Enrico , Behmoaras Jacques 
Published: December 2022

AbstractTissue fibrosis affects multiple organs and involves a master-regulatory role of macrophages which respond to an initial inflammatory insult common in all forms of fibrosis. The recently unraveled multi-organ heterogeneity of macrophages in healthy and fibrotic human disease suggest that tissue resident macrophages, expressing osteopontin (SPP1), associate with lung and liver fibrosis. However, the conservation of this SPP1+ macrophage population across different tissues, and its specificity to fibrotic diseases with different etiologies remain unclear. Integrating 13 single cell RNA-sequencing datasets to profile 225,985 tissue macrophages from healthy and fibrotic heart, lung, liver, kidney, skin and endometrium, we extended the association of SPP1+ macrophages with fibrosis to all these tissues. We also identified a subpopulation expressing matrisome-associated genes (e.g., matrix metalloproteinases and their tissue inhibitors), functionally enriched for ECM remodeling and cell metabolism, representative of a matrisome-associated macrophage (MAM) polarization state within SPP1+ macrophages. Importantly, the MAM polarization state follows a differentiation trajectory from SPP1+ macrophages, which was conserved across all fibrotic tissues and driven by NFATC1 and HIVEP3 regulons. Unlike SPP1+ macrophages, the MAM polarization state shows a positive association with ageing in mice and humans, and across multiple tissues during homeostasis. These results suggest an advanced, age-dependent polarization state of SPP1+ macrophages in fibrotic tissues as a result of prolonged inflammatory cues within each tissue microenvironment.
Integrative modeling of guanylate binding protein dimers
Authors: Schumann Wibke , Loschwitz Jennifer , Reiners Jens , Degrandi Daniel , Pfeffer Klaus , Stühler Kai , Poschmann Gereon , Smits Sander H.J. , Strodel Birgit 
Published: December 2022

AbstractGuanylate binding proteins (GBPs) are interferon-γ-activated large GTPases, effective against intracellular pathogens likeToxoplasma gondii. Their host-protective functions require oligomerization, however, the oligomer structures have not been completely resolved yet. Here, we provide dimer models for hGBP1 and the murine GBPs 2 and 7 (mGBP2 and mGBP7) based on integrative modeling that involves the crystal structure of the G domain dimer of hGBP1, cross-linking mass spectrometry (XL-MS), small angle X-ray scattering (SAXS), protein-protein docking, and molecular dynamics (MD) simulations of hGBP1, mGBP2 and mGBP7. We first compare the sequences and protein dynamics of the monomeric hGBP1, mGBP2, and mGBP7, finding that the M/E domain of all three proteins is highly mobile featuring a hinge movement, yet this motion is less pronounced in mGBP7 while its GTPase (G) domain is more flexible. These differences can be explained by the variations in the sequences between mGBP7 and hGBP1/mGBP2 and extend to their dimers. While hGBP1 and its close orthologue mGBP2 dimerize via their G domains, mGBP7 shows a variety of possible dimer structures, among them parallel and crossed-stalk conformations. The G domain is only partly involved in mGBP7 dimerization, which provides a rational why mGBP7, unlike hGBP1 and mGBP2, can dimerize in the absence of GTP. The different GBP dimer structures, which still exhibit hinge movements to certain degrees, are expected to encode diverging functions, such as a destabilization of pathogenic membranes or fusion of the parasitophorous vacuole membrane with the autophagic machinery.
Harnessing photosynthetic bacterium for light-powered biocatalysis
Authors: Zhang Yang , Yuan Jifeng 
Published: December 2022

AbstractThe traditional whole-cell biocatalysis typically utilizes the heterotrophic microbes as the biocatalyst, which requires carbohydrates to power the cofactor (ATP, NAD(P)H) regeneration. In this study, we sought to harness purple non-sulfur photosynthetic bacterium (PNSB) as the biocatalyst to achieve light-driven cofactor regeneration for cascade biocatalysis. We substantially improved the performance of PNSB-based biocatalysis by using a highly active and conditional expression system, blocking the side-reactions, controlling the feeding strategy, and attenuating the light shading effect. We found that 50 mM ferulic acid could be completely converted to vanillyl alcohol in the recombinant strain, reaching 7.7 g/L vanillyl alcohol. In addition, >99.9% conversion ofp-coumaric acid top-hydroxybenzoic alcohol (6.21 g/L) was similarly achieved under light-anaerobic conditions. Moreover, we examined the isoprenol utilization pathway (IUP) for pinene synthesis and 13.81 mM pinene (1.88 g/L) with 92.1% conversion rate from isoprenol was obtained. Taken together, these results suggested that PNSB could be a promising host for light-powered biotransformation, which offers an efficient approach for synthesizing value-added chemicals in a green and sustainable manner.
Walking bumblebees see faster
Authors: Rother Lisa , Müller Robin , Kirschenmann Erwin , Kaya-Zeeb Sinan , Thamm Markus , Pfeiffer Keram 
Published: December 2022

AbstractThe behavioral state of an animal has profound effects on neuronal information processing. Locomotion changes the response properties of visual interneurons in the insect brain, but it is still unknown if it also alters the response properties of photoreceptors. Photoreceptor responses become faster at higher temperatures. It has therefore been suggested that thermoregulation in bees and other insects could improve temporal resolution in vision, but direct evidence for this idea has so far been missing. Here we compared electroretinograms (ERGs) from the compound eyes of tethered bumblebees that were either sitting still or were walking on an air supported ball. We found that the visual processing speed strongly increased when the bumblebees were walking. By monitoring the bumblebees’ eye temperature during our recordings, we saw that the increase in response speed was in synchrony with a rise of the eye temperature. By artificially heating the bee’s head, we show that the walking induced temperature increase of the visual system is sufficient to explain the rise in processing speed. We also show that walking accelerates the visual system to the equivalent of a 14-fold increase in light intensity. We conclude that the walking-induced rise in temperature accelerates the processing of visual information in bumblebees, which is an ideal strategy to process the increased information flow during locomotion.
Hippocampal neuronal synchronization in the rat - Dissociation of perception from associative learning
Authors: Kim Kayeon , Nokia Miriam S. , Palva J. Matias , Palva Satu 
Published: December 2022

AbstractLearning requires flexible switching between perceiving and encoding external sensory stimuli, making associations with representations already stored in memory (retrieval) and acting accordingly to adapt to the environment. Hippocampus is known to be central in creating mnemonic representations, but how it could support the integration of these processes of memory encoding and retrieval during repetitive learning experiences has remained unknown. In this study, we recorded local-field potentials (LFPs) from the dorsal hippocampus during classical trace eyeblink conditioning in rats. An auditory conditioned stimulus (CS) was followed by a periorbital shock-unconditioned stimulus (US). From the LFPs, we separated hippocampal oscillations that were linked with the variation in the trial-by-trial processing of the CS from those linked with the gradual learning of the CS-US association over daily sessions of training. Short latency transient theta and gamma band oscillations were associated with learning so that both the oscillation amplitudes (strength) and phase locking increased as a function of training. In contrast, long-latency sustained alpha and beta oscillations were associated with perception of CS. These data show divergent oscillatory neural signatures for perception and learning in hippocampal subfields.
Differential transpiration between pods and leaves during stress combination in soybean
Authors: Sinha Ranjita , Shostak Benjamin , Induri Sai Preethi , Sen Sidharth , Zandalinas Sara I. , Joshi Trupti , Fritschi Felix B. , Mittler Ron 
Published: December 2022

ABSTRACTClimate change is causing an increase in the frequency and intensity of droughts, heat waves, and their combinations, diminishing agricultural productivity and destabilizing societies worldwide. We recently reported that during a combination of water deficit (WD) and heat stress (HS) stomata on leaves of soybean plants are closed, while stomata on flowers are open. This unique stomatal response was accompanied by differential transpiration (higher in flowers, while lower in leaves) that cooled flowers during a combination of WD+HS. Here we reveal that developing pods of soybean plants subjected to a combination of WD+HS use a similar acclimation strategy of differential transpiration to reduce internal pod temperature by about 4°C. We further show that enhanced expression of transcripts involved in abscisic acid degradation accompanies this response, and that preventing pod transpiration by sealing stomata causes a significant increase in internal pod temperature. Using an RNA-Seq analysis of pods developing on plants subjected to WD+HS, we also show that the response of pods to WD, HS, or WD+HS is distinct from that of leaves or flowers. Interestingly, we report that although flower, pod and seed numbers per plant are decreased under conditions of WD+HS, seed mass of plants subjected to WD+HS is larger than that of plants subjected to HS, and number of seeds with suppressed/aborted development is lower in WD+HS compared to HS. Taken together our findings reveal that differential transpiration occurs in pods of soybean plants subjected to WD+HS and that this process limits heat-induced damage to seed production.One sentence summaryDifferential transpiration between pods and leaves of soybean plants subjected to a combination of water deficit and heat stress buffers internal pod temperature.
Genome-based comparison between the recombinant SARS-CoV-2 XBB and its parental lineages
Authors: Scarpa Fabio , Sanna Daria , Azzena Ilenia , Casu Marco , Cossu Piero , Fiori Pier Luigi , Benvenuto Domenico , Imperia Elena , Giovanetti Marta , Ceccarelli Giancarlo , Cauda Roberto , Cassone Antonio , Pascarella Stefano , Ciccozzi Massimo 
Published: December 2022

AbstractRecombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM. 1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, nowadays XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability.
Neural distinctiveness and discriminability in regions of the core network representations support associative unitization
Authors: Steinkrauss A. C. , Carpenter C. M. , Tarkenton M. K. , Overman A.A. , Dennis N.A. 
Published: December 2022

AbstractPrevious work has suggested unitized pairs behave as a single unit and more critically, are processed neurally different than those of associative memories. The current works examines the neural differences between unitization and non-unitized memory using fMRI and multivoxel analyses. Specifically, we examined the differences across face-occupation pairings as a function of whether the pairing was viewed as a person performing the given job (unitized binding) or a person saying they knew someone who had a particular job (non-unitized binding). The results show that at encoding, the angular gyrus can discriminate between unitized and non-unitized target trials. Additionally, during encoding, the medial temporal lobe (hippocampus and perirhinal cortex), frontal parietal regions (angular gyrus and medial frontal gyrus) and visual regions (middle occipital cortex) exhibit distinct neural patterns to recollected unitized and non-unitized targets. Furthermore, the medial frontal gyrus and middle occipital cortex show greater neural similarity for recollected unitized trials than those of recollected non-unitized trials. We conclude that visually unitized pairs may enhance unitization in older adults due to greater similarity of trials within the same condition during the encoding process.
QRATER: a collaborative and centralized imaging quality control web-based application
Authors: Fernandez-Lozano Sofia , Dadar Mahsa , Morrison Cassandra , Manera Ana , Andrews Daniel , Rajabli Reza , Madge Victoria , St-Onge Etienne , Shafiee Neda , Livadas Alexandra , Fonov Vladimir , Collins D. Louis ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2022

AbstractQuality control (QC) is an important part of all scientific analysis, including neuroscience. With manual curation considered the gold standard, there remains a lack of available tools that make manual neuroimaging QC accessible, fast, and easy. In this article we present Qrater, a containerized web-based python application that enables viewing and rating of previously generated QC images. A group of raters with varying amounts of experience in QC evaluated Qrater in three different tasks: QC of MRI raw acquisition (10,196 images), QC of non-linear registration to a standard template (10,196 images) and QC of skull segmentation (6,968 images). We measured the proportion of failed images, timing and intra- and inter-rater agreement. Raters spent vastly different amounts of time on each image depending on their experience and the task at hand. QC of MRI raw acquisition was the slowest. While an expert rater needed approximately one minute, trained raters spent 2-6 minutes evaluating an image. The fastest was the curation of a skull segmentation image, where expert raters spent on average 3 seconds per image before assigning a rating. Rating agreement also varied depending on the experience of the raters and the task at hand: trained raters’ inter-rater agreement with the expert’s gold standard ranged from fair to substantial in raw acquisition (Cohen’s chance corrected kappa agreement scores up to 0.72) and from fair to excellent in linear registration (kappa scores up to 0.82), while the experts’ inter-rater agreement of the skull segmentation task was excellent (kappa = 0.83). These results demonstrate that Qrater is a useful asset for QC tasks that rely on manual curation of images.
AFsample: Improving Multimer Prediction with AlphaFold using Aggressive Sampling
Authors: Wallner Björn 
Published: December 2022

AbstractThe AlphaFold neural network model has revolutionized structural molecular biology with unprecedented performance. We demonstrate that by stochastically perturbing the neural network by enabling dropout at inference combined with massive sampling, it is possible to improve the quality of the generated models. We generated around 6,000 models per target compared to 25 default for AF2-multimer, with v1 and v2 multimer network models, with and without templates, and increased the number of recycles within the network. The method was benchmarked in CASP15, and compared to AF2-multimer it improved the average DockQ from 0.41 to 0.55 using identical input and was ranked at the very top in the protein assembly category when compared to all other groups participating in CASP15. The simplicity of the method should facilitate the adaptation by the field, and the method should be useful for anyone interested in modelling multimeric structures, alternate conformations or flexible structures.AvailabilityAFsample is available online athttp://wallnerlab.org/AFsample.
Diverse secondary metabolites are expressed in particle-associated and free-living microorganisms of the permanently anoxic Cariaco Basin
Authors: Geller-McGrath David , Mara Paraskevi , Taylor Gordon T. , Suter Elizabeth , Edgcomb Virginia , Pachiadaki Maria 
Published: December 2022

AbstractSecondary metabolites play essential roles in ecological interactions and nutrient acquisition, and are of interest for their potential uses in medicine and biotechnology. Under laboratory conditions the discovery of new compounds is hindered by low production, high rediscovery rates, and detection evasion. Genome mining for biosynthetic gene clusters (BGCs) is a popular approach to address these limitations, thereby uncovering often cryptic secondary metabolic potential. Marine systems are often underrepresented in bulk genome mining efforts; and habitats with unique physicochemical characteristics such as oxygen-depleted and anoxic water columns remain virtually unexplored regarding BGCs. Here, we use genome mining and differential gene expression analyses to show that redox potential and particle-associated vs. free-living lifestyles both influence the composition and production of secondary metabolites through the stratified water column of the Cariaco Basin, Venezuela. Microbiota, including understudied clades, such as Planctomycetota, encode and express a wide range of secondary metabolites in these anoxic/euxinic waters.
Photovoltaic enzymes by design and evolution
Authors: Bunzel H. Adrian , Smith James A. , Oliver Thomas A. A. , Jones Michael R. , Mulholland Adrian J. , Anderson J. L. Ross 
Published: December 2022

ABSTRACTThe global energy crisis challenges us to develop more efficient strategies for the sustainable production of energy. Given the excellent efficiency of the natural photosynthetic apparatus, biohybrid photovoltaic devices present an attractive solution for solar energy conversion. However, their composition, stability, and complexity can limit their inclusion into photovoltaic devices. Here, we combined computational design and directed evolution to overcome these limitations and create tailor-made photoenzymes. Photo-biocatalysts were designed by introducing photosensitizer binding sites into heme-containing helical bundle proteins. The designed binding sites were specific for the target photosensitizer and readily transplanted into other helical bundles. The best design was highly evolvable and reached nanomolar ligand affinity after mutagenesis and screening. The evolved enzyme generated 2.6 times higher photocurrents than the photosensitizer alone, primarily driven by increased photostability. Evolvability is a unique advantage of our protein-based approach over abiological photovoltaic and will be critical to developing efficient biohybrid systems.Abstract Figure
Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human
Authors: Schneider Simon , Kovacevic Andjela , Mayer Michelle , Dicke Ann-Kristin , Arévalo Lena , Koser Sophie A. , Hansen Jan N. , Young Samuel , Brenker Christoph , Kliesch Sabine , Wachten Dagmar , Kirfel Gregor , Strünker Timo , Tüttelmann Frank , Schorle Hubert 
Published: December 2022

AbstractCylicins are testis-specific proteins, which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 (Cylc1/CYLC1) and the autosomal Cylicin 2 (Cylc2/CYLC2)genes have been identified. Cylicins are cytoskeletal proteins with an overall positive charge due to lysine-rich repeats. While Cylicins have been localized in the acrosomal region of round spermatids, they resemble a major component of the calyx within the perinuclear theca at the posterior part of mature sperm nuclei. However, the role of Cylicins during spermiogenesis has not yet been investigated. Here, we applied CRISPR/Cas9-mediated gene-editing in zygotes to establishCylc1-andCylc2-deficient mouse lines as a model to study the function of these proteins.Cylc1deficiency resulted in male subfertility, whereasCylc2−/−,Cylc1−/yCylc2+/−, andCylc1−/yCylc2−/−males were infertile. Phenotypical characterization revealed that loss of Cylicins prevents proper calyx assembly during spermiogenesis. This results in decreased epididymal sperm counts, impaired shedding of excess cytoplasm, and severe structural malformations, ultimately resulting in impaired sperm motility. Furthermore, exome sequencing identified an infertile man with a hemizygous variant inCYLC1and a heterozygous variant inCYLC2, displaying morphological abnormalities of the sperm including the absence of the acrosome. Thus, our study highlights the relevance and importance of Cylicins for spermiogenic remodeling and male fertility in human and mouse, and provides the basis for further studies on unraveling the complex molecular interactions between perinuclear theca proteins required during spermiogenesis.