bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection
Authors: Petersen Marvin , Nägele Felix Leonard , Mayer Carola , Schell Maximilian , Petersen Elina , Kühn Simone , Gallinat Jürgen , Fiehler Jens , Pasternak Ofer , Matschke Jakob , Glatzel Markus , Twerenbold Raphael , Gerloff Christian , Thomalla Götz , Cheng Bastian 
Published: July 2022

AbstractAs SARS-CoV-2 infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 non-vaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean ± SD, 55.54 ± 7.07; median 9.7 months after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 ± 6.60) within the framework of the Hamburg City Health Study. Primary study outcomes were advanced diffusion magnetic resonance imaging (MRI) measures of white matter microstructure, cortical thickness, white matter hyperintensity load and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity and extracellular free-water which were elevated in the white matter of post-SARS-CoV-2 individuals comparing to matched controls (free-water: 0.148 ± 0.018 vs. 0.142 ± 0.017,P<.001; mean diffusivity [10−3mm2/s]: 0.747 ± 0.021 vs. 0.740 ± 0.020,P<.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.Significance statementIn this case-control study, we demonstrate that non-vaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection show significant alterations of the cerebral white matter identified by diffusion weighted imaging, such as global increases in extracellular free-water and mean diffusivity. Despite the observed brain white matter alterations in this sample, a mild to moderate SARS-CoV-2 infection was not associated with worse cognitive functions within the first year after recovery. Collectively, our findings indicate the presence of a prolonged neuroinflammatory response to the initial viral infection. Further longitudinal research is necessary to elucidate the link between brain alterations and clinical features of post-SARS-CoV-2 individuals.
Extensive gut virome variation and its associations with host and environmental factors in a population-level cohort
Authors: Nishijima Suguru , Nagata Naoyoshi , Kiguchi Yuya , Kojima Yasushi , Miyoshi-Akiyama Tohru , Kimura Moto , Ohsugi Mitsuru , Ueki Kohjiro , Oka Shinichi , Mizokami Masashi , Itoi Takao , Kawai Takashi , Uemura Naomi , Hattori Masahira 
Published: July 2022

AbstractIndigenous bacteriophage communities (virome) in the human gut have a huge impact on the gut bacterial communities (bacteriome), but virome variation at a population scale is not fully investigated yet. Here, we analyse the gut virome in a population-level cohort of 4,198 deeply phenotyped individuals. We discovered thousands of high-quality phage genomes including previously uncharacterized ones with different bacterial hosts than known major phage clades. The distribution of host bacteria was a strong determinant for the distribution of phages, and virome diversity was highly correlated with anti-viral defence mechanisms of the bacteriome, such as CRISPR-Cas and restriction-modification systems. We identified 97 various intrinsic/extrinsic factors that significantly affect the virome, including age, sex, lifestyle, and diet, most of which showed consistent associations with both phages and their predicted bacterial hosts. Among the metadata categories, disease and medication had the strongest effects on the virome structure. Overall, these results present a basis to understand the symbiotic communities of bacteria and their viruses in the human gut, which will facilitate the medical and industrial applications of indigenous viruses.
Integrative solution structure of a PTBP1-viral IRES complex reveals strong compaction and ordering with residual conformational flexibility
Authors: Dorn Georg , Gmeiner Christoph , de Vries Tebbe , Dedic Emil , Novakovic Mihajlo , Damberger Fred F. , Maris Christophe , Finol Esteban , Sarnowski Chris P. , Kohlbrecher Joachim , Welsh Timothy J. , Bolisetty Sreenath , Mezzenga Raffaele , Aebersold Ruedi , Leitner Alexander , Yulikov Maxim , Jeschke Gunnar , Allain Frédéric H.-T. 
Published: July 2022

AbstractRNA-binding proteins (RBPs) are crucial regulators of gene expression and often comprise well-defined domains interspersed by flexible, intrinsically disordered regions. The structure determination of ribonucleoprotein complexes involving such RBPs is not common practice and requires integrative structural modeling approaches due to the fact that they often do not form a single stable globular state. Here, we integrate data from magnetic resonance, mass spectrometry, and small angle scattering to determine the solution structure of the polypyrimidine-tract binding protein 1 (PTBP1 also called hnRNP I) bound to an RNA which is part of the internal ribosome entry site (IRES) of the encephalomyocarditis virus (EMCV). PTBP1 binding to this IRES element enhances translation of the viral RNA. The determined structural ensemble reveals that both RNA and protein experience a strong compaction upon complex formation, get ordered but still maintain a substantial conformational flexibility. The C-terminal RNA recognition motif (RRM4) of PTBP1 rigidifies the complex by binding a single-strand RNA linker and, in turn, is essential for IRES-mediated translation. PTBP1 acts as an RNA chaperone for the IRES, by ordering the RNA into a few discrete conformations that expose the RNA stems to the outer surface of the RNP complex for subsequent interactions with the translation machinery. The conformational diversity within this structural ensemble is likely common among RNP complexes and important for their functionality. The presented approach opens the possibility to characterize heterogeneous RNP structures at atomic level.
Glioma-derived CCL2 and CCL7 mediate migration of immune suppressive CCR2+ myeloid cells into the tumor microenvironment in a redundant manner
Authors: Takacs Gregory P. , Kreiger Christian J. , Luo Defang , Tian Guimei , Garcia Julia S. , Deleyrolle Loic P. , Mitchell Duane A. , Harrison Jeffrey K. 
Published: July 2022

AbstractGlioblastoma (GBM) is the most common and malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized in part by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive, hematopoietic cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a potent subset of myeloid cells, expressing monocytic (M)-MDSC markers, distinguished by dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate into the TME. This study evaluated the T cell suppressive function and migratory properties of CCR2+/CX3CR1+ MDSCs. Bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Recombinant and glioma-derived CCL2 and CCL7 induce the migration of CCR2+/CX3CR1+ MDSCs with similar efficacy. KR158B-CCL2 and -CCL7 knockdown murine gliomas contain equivalent percentages of CCR2+/CX3CR1+ MDSCs compared to KR158B gliomas. Combined neutralization of CCL2 and CCL7 completely blocks CCR2-expressing cell migration to KR158B cell conditioned media. High levels of CCL2 and CCL7 are also associated with negative prognostic outcomes in GBM patients. These data provide a more comprehensive understanding of the function of CCR2+/CX3CR1+ MDSCs and the role of CCL2 and CCL7 in the recruitment of these immune suppressive cells and further support the significance of targeting this chemokine axis in GBM.
Multisensory learning binds modality-specific neurons into a cross-modal memory engram
Authors: Okray Zeynep , Jacob Pedro F. , Stern Ciara , Desmond Kieran , Otto Nils , Vargas-Gutierrez Paola , Waddell Scott 
Published: July 2022

AbstractAssociating multiple sensory cues with objects and experience is a fundamental brain process that improves object recognition and memory performance. However, neural mechanisms that bind sensory features during learning and augment memory expression are unknown. Here we demonstrate multisensory appetitive and aversive memory in Drosophila. Combining colors and odors improved memory performance, even when each sensory modality was tested alone. Temporal control of neuronal function revealed visually-selective mushroom body Kenyon Cells (KCs) to be required for both enhancement of visual and olfactory memory after multisensory training. Voltage imaging in head-fixed flies showed that multisensory learning binds activity between streams of modality-specific KCs, so that unimodal sensory input generates a multimodal neuronal response. Binding occurs between regions of the olfactory and visual KC axons, which receive valence-relevant dopaminergic reinforcement, and is propagated downstream. Dopamine locally releases GABA-ergic inhibition to permit specific microcircuits within KC-spanning serotonergic neurons to function as an excitatory bridge between the previously ‘modality-selective’ KC streams. Cross-modal binding thereby expands the olfactory memory engram by recruiting visual path KCs to become odor responsive. This broadening of the engram improves memory performance after multisensory learning and permits a single sensory feature to retrieve the memory of the multimodal experience.
IL11 stimulates IL33 expression and proinflammatory fibroblast activation
Authors: Widjaja Anissa A. , Chothani Sonia , Viswanathan Sivakumar , Wei Ting Joyce Goh , Lim Wei-Wen , Cook Stuart A. 
Published: July 2022

AbstractInterleukin 11 (IL11) is upregulated in inflammatory conditions where it is believed to have anti-inflammatory activity. However, recent studies suggest instead that IL11 may promote inflammation, via the stroma. Here, we assessed whether IL11 is pro- or anti-inflammatory in fibroblasts. Primary cultures of human kidney, lung or skin fibroblasts were stimulated with IL11 that resulted in transient STAT3 phosphorylation and bi-modal ERK activation. RNA sequencing over a time course of IL11 stimulation revealed a robust short-lived transcriptional response, which was enriched for gene set hallmarks of inflammation and characterized by upregulation ofSERPINB2, TNFRSF18, IL33, CCL20, IL1RL1, CXCL3/5/8, ICAM1andIL11itself.IL33was the most upregulated signaling factor (38-fold, P=9.8×10−5) andIL1RL1, its cognate receptor, was similarly increased (18-fold, P=1.1×10−34). In proteomic studies, IL11 triggered a proinflammatory secretome with notable upregulation of IL8, IL6, MCP1, CCL20 and CXCL1/5/6, which are important chemotaxins for neutrophils, monocytes and lymphocytes. IL11 induced IL33 expression across fibroblast types and inhibition of STAT3, but not MEK/ERK, prevented this. These data establish IL11 as pro-inflammatory with specific importance for priming the IL33 alarmin response in inflammatory fibroblasts.
Armadillo repeat-containing kinesin represents the versatile plus-end-directed transporter in Physcomitrella
Authors: Yoshida Mari W. , Hakozaki Maya , Goshima Gohta 
Published: July 2022

AbstractKinesin-1, also known as conventional kinesin, is widely utilised for microtubule plus-end-directed (“anterograde”) transport of various cargos in animal cells. However, a motor functionally equivalent to the conventional kinesin has not been identified in plants, which lack the kinesin-1 genes. Here, we show that plant-specific armadillo repeat-containing kinesin (ARK) is the long sought-after versatile anterograde transporter in plants. InARKmutants of the mossPhyscomitrium patens, the anterograde motility of nuclei, chloroplasts, mitochondria, and secretory vesicles was suppressed. Ectopic expression of non-motile or tail-deleted ARK did not restore organelle distribution. Another prominent macroscopic phenotype ofARKmutants was the suppression of cell tip growth. We showed that this defect was attributed to the mislocalisation of actin regulators, including RopGEFs; expression and forced apical localisation of RopGEF3 suppressed the growth phenotype of theARKmutant. The mutant phenotypes were partially rescued by ARK homologues inArabidopsis thaliana, suggesting the conservation of ARK functions in plants.
Deciphering of BTH-induced response of tomato (Solanum lycopersicum L.) and its effect on plant virus infection through the multi-omics approach
Authors: Patryk Frąckowiak , Barbara Wrzesińska , Przemysław Wieczorek , Paloma Sanchez-Bel , Laura Kunz , Antje Dittmann , Aleksandra Obrępalska-Stęplowska 
Published: July 2022

AbstractOne of the preventive methods used to limit the losses caused by viruses is the application of synthetic immunity inducers, such as benzo(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). This study aimed to explain how the BTH treatment affects the defence and developmental processes in tomato plants (Solanum lycopersicum L.) as well as plant response to virus infection.The comparative multi-omics analyses of tomato plants treated with BTH were performed, including transcriptomics (RNA-seq), proteomics (Liquid Chromatography-Mass Spectrometry), and metabolomics (targeted hormonal analysis). To confirm the priming effect of BTH on tomato resistance, the plants were infected with tomato mosaic virus (ToMV) seven days post-BTH treatment.The combined functional analysis indicated the high impact of BTH on the plant’s developmental processes and activation of the immune response early after the treatment. In the presented experimental model, the increased level of WRKY TRANSCRIPTION FACTORS, ARGONAUTE 2A, thiamine and glutathione metabolism, cell wall reorganization, and detoxification processes, as well as accumulation of three phytohormones: abscisic acid, jasmonic-isoleucine (JA-Ile), and indole-3-carboxylic acid (I3CA), were observed upon BTH application.The immune response activated by BTH was related to increased expression of genes associated with the cellular detoxification process, systemic acquired resistance, and induced systemic resistance as well as post-transcriptional gene silencing. Increased levels of I3CA and JA-Ile might explain the BTH’s effectiveness in the induction of the plant defence against a broad spectrum of pathogens. For the first time, the BTH impact on the thiamine metabolism was revealed in tomatoes.
Transcriptional drifts associated with environmental changes in endothelial cells
Authors: Afshar Yalda , Ma Feiyang , Quach Austin , Jeong Anhyo , Sunshine Hannah Louise , Freitas Vanessa , Jami-Alahmadi Yasaman , Li Xinmin , Pellegrini Matteo , Wohlschlegel James , Romanoski Casey E. , Iruela-Arispe M. Luisa 
Published: July 2022

AbstractEnvironmental cues, such as physical forces and heterotypic cell interactions play a critical role in cell function, yet their collective contributions to transcriptional changes are unclear. Focusing on human endothelial cells, we performed broad individual sample analysis to identify transcriptional drifts associated with environmental changes that were independent of genetic background. Global gene expression profiling by RNA-seq and protein expression by LC-MS directed proteomics distinguished endothelial cells in vivo from genetically matched culture (in vitro) samples. Over 43% of the transcriptome was significantly changed by the in vitro environment. Subjecting cultured cells to long-term shear stress significantly rescued the expression of approximately 17% of genes. Inclusion of heterotypic interations by co-culture of endothelial cells with smooth muscle cells normalized approximately 9% of the original in vivo signature. We identify novel flow depedent genes, as well as, genes that necessitate heterotypic cell interactions to mimic the in vivo transcriptome. Our findings highlight specific genes and pathways that rely on contextual information and physical forces.
Gut microbiota and holobiont metabolome composition of the Medaka fish (Oryzias latipes) are affected by a short exposure to the cyanobacterium Microcystis aeruginosa
Authors: Foucault Pierre , Gallet Alison , Duval Charlotte , Marie Benjamin , Duperron Sébastien 
Published: July 2022

AbstractBlooms of toxic cyanobacteria are a common stress encountered by aquatic fauna. Evidence indicates that long-lasting blooms affect fauna-associated microbiota. Because of their multiple roles, host-associated microbes are nowadays considered relevant to ecotoxicology, yet the respective timing of microbiota versus functional changes in holobionts response needs to be clarified. The response of gut microbiota and holobiont’s metabolome to exposure to a dense culture of Microcystis aeruginosa was investigated as a microcosm-simulated bloom in the model fish species Oryzias latipes (medaka). Both gut microbiota and gut metabolome displayed significant composition changes after only 2 days of exposure. A dominant symbiont, member of the Firmicutes, plummeted whereas various genera of Proteobacteria and Actinobacteriota increased in relative abundance. Changes in microbiota composition occurred earlier and faster compared to metabolome composition, suggesting that the microbiota drives the holobiont’s response. Liver and muscle metabolome were much less affected than guts, supporting that gut and associated microbiota are in the front row upon exposure. This study highlights that even short cyanobacterial blooms, that are increasingly frequent, trigger changes in microbiota composition and holobiont metabolome. It emphasizes the relevance of multi-omics approaches to explore organism’s response to an ecotoxicological stress.Graphical abstractHighlights-A 2-day exposure to a simulated M. aeruginosa bloom is enough to sharply decrease the Firmicute/Proteobacteria ratio in the gut of Oryzias latipes fish.-The exposure induced changes in metabolome composition after 2 days in the gut and 4 days in the liver.-The gut bacterial microbiota response occurred faster than metabolome’s; we hypothesize that changes in gut microbiota may drive the gut metabolome compositional changes.
CENP-A and CENP-B collaborate to create an open centromeric chromatin state
Authors: Nagpal Harsh , Fierz Beat 
Published: July 2022

AbstractCentromeres, the sites within chromosomes responsible for accurate genome repartitioning, are epigenetically defined via replacement of canonical histone H3 by the histone variant CENP-A forming specific nucleosomes with increased DNA flexibility. In human cells, CENP-A nucleosomes and thus centromeres localize to genomic regions containing extended tandem repeats of alpha-satellite DNA. There, the constitutive centromere associated network (CCAN) and the kinetochore assemble, connecting the centromere to spindle microtubules during cell division. CENP-A provides a major recruitment point for many CCAN member proteins. One factor, CENP-B, binds to a specific DNA sequence contained in about half of alpha-satellite repeats. CENP-B is a dimer and is involved in maintaining centromere stability and, together with CENP-A, shapes the basic layer of the centromeric chromatin state. While recent studies have revealed the structure of large parts of the CCAN complexes, the nanoscale organization of centromeric chromatin is not well understood.Here, we use single-molecule fluorescence resonance energy transfer (FRET) and colocalization imaging as well as dynamic experiments in cells to show that CENP-A incorporation establishes a far more dynamic and open chromatin state compared to canonical H3. We investigate whether CENP-A marks a landing spot for CENP-B, and find that on the single nucleosome level, CENP-B does not prefer H3 over CENP-A nucleosomes. However, in a chromatin fiber context, CENP-B binding is suppressed by higher-order chromatin structure. The increased dynamics of CENP-A chromatin create an opening, allowing CENP-B access and binding. In turn, bound CENP-B further opens the chromatin fiber structure, potentially via bending the bound DNA. Finally, transient knockdown of CENP-A expression in cells increases CENP-B mobility in cells. Together, our studies show that the two centromere-specific proteins collaborate to reshape chromatin structure, enabling the binding of centromeric factors and establishing a centromeric chromatin state.
Increased mitochondrial Ca2+ contributes to health decline with age and Duchene muscular dystrophy in C. elegans
Authors: Higashitani Atsushi , Teranishi Mika , Nakagawa Yui , Itoh Yukou , Sudevan Surabhi , Szewczyk Nathaniel J , Kubota Yukihiko , Abe Takaaki , Kobayashi Takeshi 
Published: July 2022

SummarySarcopenia is a geriatric syndrome characterized by an age-related decline in skeletal muscle mass and strength. Here, we show that suppression of mitochondrial calcium uniporter (MCU)-mediated Ca2+ influx into mitochondria in the body wall muscles of the nematode Caenorhabditis elegans improved the sarcopenic phenotypes, blunting movement and mitochondrial structural and functional decline with age. We found that normally aged muscle cells exhibited elevated resting mitochondrial Ca2+ levels and increased mitophagy to eliminate damaged mitochondria. Similar to aging muscle, we found that suppressing MCU function in muscular dystrophy improved movement via reducing elevated resting mitochondrial Ca2+ levels. Taken together, our results reveal that elevated resting mitochondrial Ca2+ levels contribute to muscle decline with age and in muscular dystrophy. Further, modulation of MCU activity may act as a potent pharmacological target in various conditions involving muscle loss.