bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical utility of measuring CD4+T follicular cells in patients with immune dysregulation
Authors: LaBere Brenna , Nguyen Alan A. , Habiballah Saddiq B. , Elkins Megan , Imperial Juliet , Li Betty , Devana Sridevi , Timilsina Suraj , Stubbs Spencer B. , Joerger Jill , Chou Janet , Platt Craig D. 
Published: June 2023

ABSTRACTMechanistic studies of autoimmune disorders have identified circulating T follicular helper (cTfh) cells as drivers of autoimmunity. However, the quantification of cTfh cells is not yet used in clinical practice due to the lack of age-stratified normal ranges and the unknown sensitivity and specificity of this test for autoimmunity. We enrolled 238 healthy participants and 130 patients with common and rare disorders of autoimmunity or autoinflammation. Patients with infections, active malignancy, or any history of transplantation were excluded. In 238 healthy controls, median cTfh percentages (range 4.8% – 6.2%) were comparable among age groups, sexes, races, and ethnicities, apart from a significantly lower percentages in children less than 1 year of age (median 2.1%, CI: 0.4% – 6.8,p<0.0001). Among 130 patients with over 40 immune regulatory disorders, a cTfh percentage exceeding 12% had 88% sensitivity and 94% specificity for differentiating disorders with adaptive immune cell dysregulation from those with predominantly innate cell defects. This threshold had a sensitivity of 86% and specificity of 100% for active autoimmunity and normalized with effective treatment. cTfh percentages exceeding 12% distinguish autoimmunity from autoinflammation, thereby differentiating two endotypes of immune dysregulation with overlapping symptoms and different therapies.
Localized and global representation of prior value, sensory evidence, and choice in male mouse cerebral cortex
Authors: Ishizu Kotaro , Nishimoto Shosuke , Ueoka Yutaro , Funamizu Akihiro 
Published: June 2023

AbstractAdaptive behavior requires integrating prior knowledge of action outcomes and sensory evidence for making decisions while maintaining prior knowledge for future actions. As outcome- and sensory-based decisions are often tested separately, it is unclear how these processes are integrated in the brain. In a tone frequency discrimination task with two sound durations and asymmetric reward blocks, we found that neurons in the medial prefrontal cortex of male mice represented the additive combination of prior reward expectations and choices. The sensory inputs and choices were selectively decoded from the auditory cortex irrespective of reward priors and the secondary motor cortex, respectively, suggesting localized computations of task variables are required within single trials. In contrast, all the recorded regions represented prior values that needed to be maintained across trials. We propose localized and global computations of task variables in different time scales in the cerebral cortex.
Whole Genome Sequencing Reveals Autooctoploidy in the Chinese Sturgeon and its Evolutionary Trajectories
Authors: Wang Binzhong , Wu Bin , Liu Xueqing , Hu Yacheng , Ming Yao , Bai Mingzhou , Liu Juanjuan , Xiao Kan , Zeng Qingkai , Yang Jing , Wang Hongqi , Guo Baifu , Tan Chun , Hu Zixuan , Zhao Xun , Li Yanhong , Yue Zhen , Mei Junpu , Jiang Wei , Yang Yuanjin , Li Zhiyuan , Gao Yong , Chen Lei , Jian Jianbo , Du Hejun 
Published: June 2023

AbstractThe Order Acipenseriformes, which include sturgeons and paddlefishes, represent “living fossils” with complex genomes that are good models for understanding whole genome duplication (WGD) and ploidy evolution in fishes. Here we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploidAcipenser sinensis(Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show thatA. sinensisis a complex autooctoploid species containing four kinds of octovalents (8 n), a hexavalent (6 n), two tetravalents (4 n), and a divalent (2 n). We propose based on an analysis taking into account delayed rediploidization that its octoploid genome composition results from two rounds of homologous whole genome duplications (WGDs), and further provide insight into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy composition and evolutionary trajectories of polyploidy fishes.
TheToxoplasmamonocarboxylate transporters are involved in the metabolism within the apicoplast and are linked to parasite survival
Authors: Dong Hui , Yang Jiong , He Kai , Zheng Wen-Bin , Lai De-Hua , Liu Jing , Ding Hui-Yong , Wu Rui-Bin , Brown Kevin M. , Hide Geoff , Lun Zhao-Rong , Zhu Xing-Quan , Long Shaojun 
Published: June 2023

AbstractThe apicoplast is a four-membrane plastid found in the apicomplexans, which harbors biosynthesis and organelle housekeeping activities in the matrix. However, the mechanism driving the flux of metabolites, in and out, remains unknown. Here we used TurboID and genome engineering to identify apicoplast transporters inToxoplasma gondii. Among the many novel transporters, we show that one pair of apicomplexan monocarboxylate transporters (AMTs) appears to have evolved from a putative host cell that engulfed a red alga. Protein depletion showed that AMT1 and AMT2 are critical for parasite growth. Metabolite analyses supported the notion that AMT1 and AMT2 are associated with biosynthesis of isoprenoids and fatty acids. However, stronger phenotypic defects were observed for AMT2, including in the inability to establishT. gondiiparasite virulence in mice. This study clarifies, significantly, the mystery of apicoplast transporter composition and reveals the importance of the pair of AMTs in maintaining the apicoplast activity in apicomplexans.
Reversible translocation of acyl-CoA:cholesterol acyltransferase (ACAT) between the endoplasmic reticulum and vesicular structures
Authors: Schiffmann Andrea , Ahlswede Lena , Gimpl Gerald 
Published: June 2023

ABSTRACTThe enzyme acyl-CoA:cholesterol acyltransferase (ACAT) is normally localized in the endoplasmic reticulum (ER) where it can esterify cholesterol for storage in lipid droplets and/or the formation of lipoproteins. Here, we report that ACAT can translocate from the ER into vesicular structures in response to different ACAT inhibitors. The translocation was fast (within minutes), reversible and occurred in different cell types. Interestingly, oleic acid was able to fasten the re-translocation from vesicles back into the reticular ER network. The process of ACAT translocation could also be induced by cyclodextrins, cholesterol, lanosterol (but not 4-cholestene-3 one), 25-hydroxycholesterol, and by certain stress stimuli such as hyperosmolarity (sucrose treatment), temperature change, or high-density cultivation.In vitroesterification showed that ACAT remains fully active after it has been translocated to vesicles in response to hyperosmotic sucrose treatment of the cells. The translocation process was not accompanied by changes in the electrophoretic mobility of ACAT, even after chemical crosslinking. Interestingly, the protein synthesis inhibitor cycloheximide showed a stimulating effect on ACAT activity and prevented the translocation of ACAT from the ER into vesicles. The translocation process of ACAT may provide a new way to regulate cholesterol esterification in cells, by altering the accessibility of the enzyme to its substrate.
The acidic intrinsically disordered region of the inflammatory mediator HMGB1 mediates fuzzy interactions with chemokine CXCL12
Authors: Mantonico Malisa Vittoria , Leo Federica De , Quilici Giacomo , Colley Liam , Marchis Francesco De , Crippa Massimo , Schulte Tim , Zucchelli Chiara , Ricagno Stefano , Giachin Gabriele , Ghitti Michela , Bianchi Marco , Musco Giovanna 
Published: June 2023

AbstractChemokines engage in heterodimeric interactions to activate or dampen their cognate receptors in inflammatory conditions. The chemokine CXCL12 forms with the alarmin HMGB1 a patho-physiologically relevant heterocomplex (HMGB1●CXCL12), whose formation synergically promotes the inflammatory response elicited by the G-protein coupled receptor CXCR4. However, the molecular details of complex formation were still elusive. Through an integrative structural approach (NMR, AUC, ITC, MST, SAXS) we show that HMGB1●CXCL12 represents the firstfuzzychemokines heterocomplex reported so far. HMGB1 and CXCL12 form a dynamic equimolar assembly, rather than involving one HMGB1 and two CXCL12 molecules as previously assumed, with structured and unstructured HMGB1 regions recognizing the dimerization surface of CXCL12. We uncover an unexpected role of the acidic intrinsically disordered region (IDR) in heterocomplex formation and provide the first evidence that the acidic IDR facilitates the ternary HMGB1•CXCL12•CXCR4 interaction on the cell surface. Thus, the interaction of HMGB1 with CXCL12 diverges radically from the classical rigid heterophilic chemokine-chemokine dimerization. Simultaneous interference with the multiple interactions within HMGB1●CXCL12 complex formation might offer novel pharmacological strategies to inhibit its detrimental activity in inflammatory conditions.
Distinct subtypes of grey matter heterotopia show subtype-specific morpho-electric neuronal properties and dynamics of epileptiform activity in mice
Authors: Vermoyal Jean-Christophe , Hardy Delphine , Goirand-Lopez Lucas , Vinck Antonin , Silvagnoli Lucas , Fortoul Aurélien , Francis Fiona , Cappello Silvia , Bureau Ingrid , Represa Alfonso , Cardoso Carlos , Watrin Françoise , Marissal Thomas , Manent Jean-Bernard 
Published: June 2023

AbstractGrey matter heterotopia (GMH) are neurodevelopmental disorders associated with abnormal cortical function and epilepsy. Subcortical band heterotopia (SBH) and periventricular nodular heterotopia (PVNH) are two well-recognized GMH subtypes in which neurons are misplaced, either forming nodules lining the ventricles in PVNH, or forming bands in the white matter in SBH. Although both PVNH and SBH are commonly associated with epilepsy, it is unclear whether these two GMH subtypes differ in terms of pathological consequences or, on the contrary, share common altered mechanisms. Here, we studied two robust preclinical models of SBH and PVNH, and performed a systematic comparative assessment of the physiological and morphological diversity of heterotopia neurons, as well as the dynamics of epileptiform activity and input connectivity. We uncovered a complex set of altered properties, including both common and distinct physiological and morphological features across heterotopia subtypes, and associated with specific dynamics of epileptiform activity. Taken together, these results suggest that pro-epileptic circuits in GMH are, at least in part, composed of neurons with distinct, subtype-specific, physiological and morphological properties depending on the heterotopia subtype. Our work supports the notion that GMH represent a complex set of disorders, associating both shared and diverging pathological consequences, and contributing to forming epileptogenic networks with specific properties. A deeper understanding of these properties may help to refine current GMH classification schemes by identifying morpho-electric signatures of GMH subtypes, to potentially inform new treatment strategies.
New viruses ofCladosporiumsp. expand considerably the taxonomic structure ofGammapartitivirusgenus
Authors: Jaccard Augustine , Dubuis Nathalie , Kellenberger Isabelle , Brodard Justine , Schnee Sylvain , Gindro Katia , Schumpp Olivier 
Published: June 2023

AbstractDespite the fact thatCladosporiumsp. are ubiquitous fungi, their viromes have been little studied. By analysing a collection of Cladosporium fungi, two new partitiviruses named Cladosporium cladosporioides partitivirus 1 (CcPV1) and Cladosporium cladosporioides partitivirus 2 (CcPV2) co-infecting a strain ofCladosporium cladosporioideswere identified. Their complete genome consists in two monocistronic dsRNA segments (RNA1 and RNA2) with a high percentage of pairwise identity on 5’ and 3’ end. The RNA dependant RNA polymerase (RdRp) of both viruses and the capsid protein (CP) of CcPV1 display the classic characteristics required for their assignment to theGammapartitivirusgenus. In contrast, CcPV2 RNA2 encodes for a 41 KDa CP that is unusually small with a low percentage of amino acid identity as compared to CPs of other viruses classified in this genus. This sequence was used to annotate fifteen similar viral sequences with unconfirmed function. The phylogeny of the CP was highly consistent with the phylogeny of their corresponding RdRp, supporting the organization of gammapartitiviruses into three distinct clades despite stretching the current demarcation criteria.
When Neural Activity Fails to Reveal Causal Contributions
Authors: Fakhar Kayson , Dixit Shrey , Hadaeghi Fatemeh , Kording Konrad P. , Hilgetag Claus C. 
Published: June 2023

AbstractNeuroscientists rely on distributed spatio-temporal patterns of neural activity to understand how neural units contribute to cognitive functions and behavior. However, the extent to which neural activity reliably indicates a unit’s causal contribution to the behavior is not well understood. To address this issue, we provide a systematic multi-site perturbation framework that captures time-varying causal contributions of elements to a collectively produced outcome. Applying our framework to intuitive toy examples and artificial neuronal networks revealed that recorded activity patterns of neural elements may not be generally informative of their causal contribution due to activity transformations within a network. Overall, our findings emphasize the limitations of inferring causal mechanisms from neural activities and offer a rigorous lesioning framework for elucidating causal neural contributions.
The Time-Course of Food Representation in the Human Brain
Authors: Moerel Denise , Psihoyos James , Carlson Thomas A. 
Published: June 2023

ABSTRACTHumans make decisions about food every day. The visual system provides important information that forms a basis for these food decisions. Although previous research has focused on visual object and category representations in the brain, it is still unclear how visually presented food is encoded by the brain. Here, we investigate the time-course of food representations in the brain. We used time-resolved multivariate analyses of electroencephalography (EEG) data, obtained from human participants (both sexes), to determine which food features are represented in the brain, and whether focused attention is needed for this. We recorded EEG while participants engaged in one of two tasks. In one task the stimuli were task relevant, whereas in the other task the stimuli were not task relevant. Our findings indicate that the brain can differentiate between food and non-food items from approximately 112 milliseconds after stimulus onset. The neural signal at later latencies contained information about food naturalness, how much the food was transformed, as well as the perceived caloric content. This information was present regardless of the task. Information about whether food is immediately ready to eat, however, was only present when the food was task relevant and presented at a slow presentation rate. Furthermore, the recorded brain activity correlated with the behavioural responses in an odd-item-out task. The fast representation of these food features, along with the finding that this information is used to guide food categorisation decision-making, suggests that these features are important dimensions along which the representation of foods is organised.
Maturation-dependent changes in cortical and thalamic activity during slow waves of light sleep: insights from a combined EEG-fMRI study
Authors: Bergamo Damiana , Handjaras Giacomo , Petruso Flavia , Talami Francesca , Ricciardi Emiliano , Benuzzi Francesca , Vaudano Anna Elisabetta , Meletti Stefano , Bernardi Giulio , Betta Monica 
Published: June 2023

AbstractINTRODUCTIONStudies using scalp EEG have shown that slow waves (0.5-4 Hz), the most prominent hallmark of NREM sleep, undergo relevant changes from childhood to adulthood, mirroring brain structural modifications and the acquisition of cognitive skills. Here we used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes.METHODSWe analyzed data from 14 school-age children with self-limited focal epilepsy of childhood who fell asleep during EEG-fMRI recordings. Brain regions associated with slow-wave occurrence were identified using a voxel-wise regression that also modeled interictal epileptic discharges and sleep spindles. At the group level, a mixed-effects linear model was used. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults.RESULTSSlow waves were associated with hemodynamic-signal decreases in bilateral somatomotor areas. Such changes extended more posteriorly relative to those in adults. Moreover, the involvement of areas belonging to the default mode network changes as a function of age. No significant hemodynamic responses were observed in subcortical structures. However, we identified a significant correlation between age and thalamic hemodynamic changes.CONCLUSIONSPresent findings indicate that the somatomotor cortex may have a key role in slow-wave expression throughout the lifespan. At the same time, they are consistent with a posterior-to-anterior shift in slow-wave distribution mirroring brain maturational changes. Finally, our results suggest that slow-wave changes may not reflect only neocortical modifications but also the maturation of subcortical structures, including the thalamus.Statement of significanceLow spatial resolution of conventional EEG has widely limited the possibility of accurately determining in humans the role of different brain structures in the expression of sleep slow waves throughout development. Here, for the first time, we took advantage of a simultaneous EEG-fMRI approach to accurately describe the cortical and subcortical hemodynamic correlates of sleep slow waves in a sample of 14 school-aged children. In order to elucidate age-dependent changes, we qualitatively compared present findings with those previously obtained in a group of adults. Overall our results have important implications for the understanding of how cortico-cortical and subcortico-cortical interactions shape sleep slow waves across development.
Epsilon tubulin is an essential determinant of microtubule-based structures in male germ cells
Authors: Stathatos G. Gemma , Merriner D. Jo , O’Connor Anne E. , Zenker Jennifer , Dunleavy Jessica E.M. , O’Bryan Moira K. 
Published: June 2023

AbstractAlpha, beta and gamma tubulins are essential building blocks for all eukaryotic cells. The functions of the non-canonical tubulins, delta, epsilon and zeta, however, remain poorly understood and their requirement in mammalian development untested. Herein we have used a spermatogenesis model to define epsilon tubulin (TUBE1) function in mice. We show that TUBE1 is essential for the function of multiple complex microtubule arrays, including the meiotic spindle, axoneme and manchette and in its absence, there is a dramatic loss of germ cells and male sterility. Through examining axoneme structure, we identify differences in TUBE1 function between somatic and germ cells and potentially between species. Moreover, we provide evidence for the interplay between TUBE1 and katanin-mediated microtubule severing, and for the sub-specialization of individual katanin paralogs in the regulation of specific microtubule arrays.
A Simulation Study on High Spatio-Temporal Resolution Acousto-Electrophysiological Neuroimaging
Authors: Schoeters Ruben , Tarnaud Thomas , Martens Luc , Tanghe Emmeric 
Published: June 2023

AbstractAcousto-electrophysiological neuroimaging is a technique hypothesized to record electrophysiological activity of the brain with millimeter spatial and sub-millisecond temporal resolution. This improvement is obtained by tagging areas with focused ultrasound (fUS). Due to mechanical vibration with respect to the measuring electrodes, the electrical activity of the marked region will be modulated onto the ultrasonic frequency. The region’s electrical activity can subsequently be retrieved via demodulation of the measured signal. In this study, the feasibility of this hypothesized technique is tested. This is done by calculating the forward electroencephalography (EEG) response under quasi-static assumptions. The head is simplified as a set of concentric spheres. Two sizes are evaluated representing human and mouse brains. Moreover, feasibility is assessed for wet and dry transcranial, and for cortically placed electrodes. The activity sources are modeled by dipoles, with their current intensity profile drawn from a power-law power spectral density. It is shown that mechanical vibration modulates the endogenous activity onto the ultrasonic frequency. The signal strength depends non-linearly on the alignment between dipole orientation, vibration direction and recording point. The strongest signal is measured when these three dependencies are perfectly aligned. The signal strengths are in the pV-range for a dipole moment of 5 nAm and ultrasonic pressures within FDA-limits. The endogenous activity can then be accurately reconstructed via demodulation. Two interference types are investigated: vibrational and static. Depending on the vibrational interference, it is shown that millimeter resolution signal detection is possible also for deep brain regions. Subsequently, successful demodulation depends on the static interference, that at MHz-range has to be sub-picovolt.
Glucocorticoid stress hormones stimulate vesicle-free Tau secretion and spreading in the brain
Authors: Yu Qing , Du Fang , Belli Irla , Gomes Patricia A. , Sotiropoulos Ioannis , Waites Clarissa L. 
Published: June 2023

SummaryChronic stress and elevated levels of glucocorticoids (GCs), the main stress hormones, accelerate Alzheimer’s disease (AD) onset and progression. A major driver of AD progression is the spreading of pathogenic Tau protein between brain regions, precipitated by neuronal Tau secretion. While stress and high GC levels are known to induce intraneuronal Tau pathology (i.e.hyperphosphorylation, oligomerization) in animal models, their role in trans-neuronal Tau spreading is unexplored. Here, we find that GCs promote secretion of full-length, vesicle-free, phosphorylated Tau from murine hippocampal neurons andex vivobrain slices. This process occurs via type 1 unconventional protein secretion (UPS) and requires neuronal activity and the kinase GSK3β. GCs also dramatically enhance trans-neuronal Tau spreadingin vivo, and this effect is blocked by an inhibitor of Tau oligomerization and type 1 UPS. These findings uncover a potential mechanism by which stress/GCs stimulate Tau propagation in AD.