bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles
Authors: Brahmer Alexandra , Geiß Carsten , Lygeraki Andriana , Neuberger Elmo , Tzaridis Theophilos , Nguyen Tinh Thi , Luessi Felix , Régnier-Vigouroux Anne , Hartmann Gunther , Simon Perikles , Endres Kristina , Bittner Stefan , Reiners Katrin S , Krämer-Albers Eva-Maria 
Published: July 2023

AbstractExtracellular vesicles (EVs) derived from the CNS are potential liquid-biopsy markers for early detection and monitoring of neurodegenerative diseases and brain tumors. This study assessed the performance of a bead-based flow cytometry assay (EV Neuro) for multiparametric detection of CNS-derived EVs and identification of disease-specific markers. Different sample materials and EV isolation methods were compared. Glioblastoma- and primary human astrocyte-derived EVs exhibited distinct EV profiles, with signal intensities increasing with higher EV input. Analysis of serum or plasma from glioblastoma, multiple sclerosis, Alzheimer’s Disease patients and healthy controls showed varying marker signal intensities. Notably, data normalization improved marker identification. Specific EV populations, such as CD36+EVs in glioblastoma and GALC+EVs in multiple sclerosis, were significantly elevated in disease compared to controls. Clustering analysis techniques effectively differentiated glioblastoma patients from controls. A potential correlation between CD107a+EVs and neurofilament levels in the blood was identified in multiple sclerosis patients. Together, the semi-quantitative EV Neuro assay demonstrated its utility for EV profiling in complex samples. However, reliable statistical results in biomarker studies require large sample cohorts and high effect sizes. Nonetheless, this exploratory trial confirmed the feasibility of discovering EV-associated biomarkers and monitoring circulating EV profiles in CNS diseases using the EV Neuro assay.
Proteomic analysis reveals APOE isoform-specific regulation of ribosomes in neural precursor cells
Authors: Srividya M , Paul Pradip , Ramakrishna Sarayu , Ghose Vivek , Dey Gourav , Muddashetty Ravi S , Jain Sanjeev , Purushottam Meera , Viswanath Biju , Sud Reeteka 
Published: July 2023

ABSTRACTApoE4 isoform contributes to increased risk for Alzheimer’s Disease (AD) over the life course of individuals. Much remains unknown about the biological pathways that connectAPOE4genotype with the development of pathology that eventually leads to AD, nor do we know how early in life these cellular alterations begin. To answer these questions, we derived neural precursor cells (NPCs) from induced pluripotent stem cells (IPSCs) that were CRISPR-edited at theAPOElocus. We intended to characterize the protein expression landscape in the NPCs subsequent to targeted deletion of E4 from a parent IPSC line ofAPOE3/4genotype. Differentially expressed proteins (DEPs) following mass spectrometric analysis were determined from the protein abundance fold change values obtained for each protein. Proteins which showed >1.5-fold difference with FDR adjusted P-value < 0.05 were considered differentially expressed. DEPs were mapped to the STRING database (v11.5) for retrieval of interacting proteins and functional enrichment. CRISPR-editing of E4 from the parent line revealed 98 differential expressed proteins. Of these, 54 were upregulated, and 44 were downregulated. Further analysis of the DEPs via STRING database showed that these changes primarily affect pathways linked to RNA processing, plasma membrane repair, and cytoskeleton organization. Indeed, we find the effects of E4 extend beyond proteins considered central to AD pathology. Knowing more about the protein interactions regulated by ApoE, in an isoform-specific manner, can reveal new mechanistic insights into development of AD.
A single cell atlas of sexual development inPlasmodium falciparum
Authors: Dogga Sunil Kumar , Rop Jesse C. , Cudini Juliana , Farr Elias , Dara Antoine , Ouologuem Dinkorma , Djimde Abdoulaye A. , Talman Arthur M. , Lawniczak Mara K.N. 
Published: July 2023

AbstractThe developmental decision made by malaria parasites to become sexual underlies all malaria transmission. Here, we describe a rich atlas of short and long-read single-cell transcriptomes of over 37,000Plasmodium falciparumcells across intraerythrocytic asexual and sexual development. We used the atlas to explore transcriptional modules and exon usage along sexual development, and expanded it to include malaria parasites collected from a Malian individual naturally infected with multipleP. falciparumstrains. We investigated genotypic and transcriptional heterogeneity within and among these wild strains at a single-cell level for the first time, finding considerable differential expression between different strains even within the same host. This work is a key addition to the Malaria Cell Atlas, enabling a deeper understanding of the biology and diversity of transmission stages.One sentence summaryThis addition to the Malaria Cell Atlas presents an analysis of sexual development and uses it to explore a natural infection.
Correlative superresolution microscopy with deep UV reactivation
Authors: Prakash Kirti 
Published: July 2023

AbstractCorrelative superresolution microscopy has the potential to accurately visualize and validate new biological structures past the diffraction limit. However, combining different superresolution modalities, such as deterministic stimulated emission depletion (STED) and stochastic single-molecule localization microscopy (SMLM), is a challenging endeavor. For correlative STED and SMLM, the following poses a significant challenge: (1) the photobleaching of the fluorophores in STED; (2) the subsequent reactivation of the fluorophores for SMLM; and (3) finding the right fluorochrome and imaging buffer for both imaging modalities. Here, we highlight how the deep ultraviolet (DBUE) wavelengths of the Mercury (Hg) arc lamp can help recover STED bleaching and allow for the reactivation of single molecules for SMLM imaging. We also show that Alexa Fluor 594 and the commercially available Prolong Diamond turn out to be excellent fluorophores and imaging media for correlative STED and SMLM.
Amphibian segmentation clock models suggest mechanisms of slowed development across increasing genome size and nuclear volume
Authors: Taylor Alexandra Nicole , Mueller Rachel Lockridge , Prasad Ashok 
Published: July 2023

AbstractEvolutionary increases in genome size, cell volume, and nuclear volume have been observed across the tree of life, with positive correlations documented between all three traits. Developmental tempo slows as genomes, nuclei, and cells increase in size, yet the driving mechanisms are poorly understood. To bridge this gap, we use a mathematical model of the somitogenesis clock to link slowed developmental tempo with changes in intra-cellular gene expression kinetics induced by increasing genome size and nuclear volume. We adapt a well-known somitogenesis clock model to two model amphibian species that vary ten-fold in genome size:Xenopus laevis(3.2 Gb) andAmbystoma mexicanum(32 Gb). Based on simulations and backed by analytical derivations, we identify parameter changes originating from increased genome and nuclear size that slow gene expression kinetics. We simulate biological scenarios for which these parameter changes mathematically recapitulate slowed gene expression inA. mexicanumrelative toX. laevis, and we consider scenarios for which additional alterations in gene product stability and chromatin packing are necessary. Results suggest that slowed degradation rates as well as changes induced by increasing nuclear volume, which remain relatively unexplored, are significant drivers of slowed developmental tempo.
Distinct ossification trade-offs illuminate the shoulder girdle reconfiguration at the water-to-land transition
Authors: Wei Janet , Wood Thomas W.P. , Flaherty Kathleen , Enny Alyssa , Andrescavage Ali , Brazer Danielle , Navon Dina , Stewart Thomas A. , Cohen Hannah , Shanabag Anusha , Kuroda Shunya , Braasch Ingo , Nakamura Tetsuya 
Published: July 2023

AbstractThe mechanisms of the pectoral girdle transformation at the origin of terrestrial locomotion in vertebrates remains an outstanding problem in evolutionary biology1. The loss of dermal bones and the enlargement of endochondral bones resulted in the disarticulation of the pectoral girdle from the skull and the formation of the neck during the fish-to-tetrapod transition2–5. Despite the functional implications of this skeletal shift in the emergence of terrestrial vertebrates, the underlying genetic-developmental alterations have remained enigmatic. Here, we discovered that in zebrafish pectoral girdle mesodermal cells expressinggli3, a transcription factor in the Hedgehog signaling pathway, contribute to both dermal and endochondral bones. We show that Gli3 regulates expression ofactivin A receptor type 1-like, a BMP type 1 receptor lost in tetrapod lineages, and thereby determines endochondral and dermal ossification. Intriguingly, Gli and Hedgehog compound knockout fish exhibited an unexpected combination of actinopterygian fish and stem-tetrapod pectoral girdle characteristics. These ontogenetic and anatomical data suggest that a trade-off between the two distinct ossification pathways is a deeply embedded developmental program in bony fishes, with potential for tuning of this trade-off to generate novel pectoral girdle forms akin to stem-tetrapods at the dawn of vertebrate terrestrialization.
Decoding familiar visual object categories in the mu rhythm oscillatory response
Authors: Bailey Kerri M , Sami Saber , Smith Fraser W 
Published: July 2023

AbstractWhilst previous research has linked attenuation of the mu rhythm to the observation of specific visual categories, and even to a potential role in action observation via a putative mirror neuron system, much of this work has not considered what specific type of information might be coded in this oscillatory response when triggered via vision. Here, we sought to determine whether the mu rhythm contains content-specific information about the identity of familiar (and also unfamiliar) graspable objects. In the present study, right-handed participants (N=27) viewed images of both familiar (apple, wine glass) and unfamiliar (cubie, smoothie) graspable objects, whilst performing an orthogonal task at fixation. Multivariate pattern analysis (MVPA) revealed significant decoding of familiar, but not unfamiliar, visual object categories in the mu rhythm response. Thus, simply viewing familiar graspable objects may automatically trigger activation of associated tactile and/or motor properties in sensorimotor areas, reflected in the mu rhythm. In addition, we report significant attenuation in the central beta band for both familiar and unfamiliar visual objects, but not in the mu rhythm. Our findings highlight how analysing two different aspects of the oscillatory response – either attenuation or the representation of information content – provide complementary views on the role of the mu rhythm in response to viewing graspable object categories.HighlightsThe Mu Rhythm oscillation contains fine-grained information about the identity of familiar, graspable objects (but not unfamiliar)This study offers evidence of a possible oscillatory marker for cross-sensory effects involving sensorimotor and visual corticesDifferent analysis techniques (univariate vs multivariate) imply different conclusions about the role of specific oscillations in the perception of graspable objectsThe alpha rhythm at occipital sites shows greater attenuation for unfamiliar objects but better representation for familiar objects consistent with sharpening accounts of Predictive Processing
From Asymptomatic to Symptomatic: Multiomics profiling of the temporal response of grapevine viral-mixed infection
Authors: Fall M.L. , Poursalavati A. , Sidibé A. , Xu D. , Lemoyne P. , Martins G.S. , Javaran V.J. , Moffett P. , Odile Carisse 
Published: July 2023

AbstractMixed viral infections are common in grapevines. However, our understanding of the factors and signaling pathways that influence the expression of viral symptoms in mixed infections is still incomplete. In a previous study, we revealed that the presence of grapevine leafroll-associated virus species in mixed infections was randomly associated with the devel-opment of virus-like symptoms. To understand what drives the timing of these virus-like symptoms in mixed infections, we used dsRNA and total RNA sequencing and metabolomic analysis to profile the viromes, metabolites, and transcripts of grapevine leaves collected at two different times of the year (summer and autumn). We demonstrated that neither viral titre nor virome composition changes were associated with symptom expression in autumn. The total phenolic content and antioxidant capacity increased in most plants except for those with early onset symptoms. According to the results of differential gene expression analysis, cell wall biosynthesis pathways were significantly downregulated in all grapevine plants infected with grapevine leafroll-associated virus 3, grapevine asteroid mosaic-associated virus, and grape-vine Pinot gris virus. In addition, polyketide pathways were significantly upregulated in all cultivars, while flavonoid precursor (e.g. abscisic acid) production was significantly reduced in plants that expressed strong virus-like symptoms. In the ‘Vidal’ cultivar, an uncharacterized double-stranded RNA-binding protein (DRB) appears to play a critical role in the plant’s an-tiviral defences, supporting the recent hypothesis that DRBs make an important contribution to dominant antiviral responses in plants. The seasonality of the expression virus-like symptoms appears to be a consequence of the dynamic interactions between antiviral factors and viral counter-defences that occur at different developmental stages of grapevine.
Structural insights into complex I deficiency and assembly from the disease-relatedndufs4-/-mouse
Authors: Yin Zhan , Agip Ahmed-Noor A. , Bridges Hannah R. , Hirst Judy 
Published: July 2023

AbstractRespiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD+homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, thendufs4-/-mouse, to define the structural, biochemical and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of mouse-heartndufs4-/-complex I revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12 (that replaces its paralogue NDUFAF2 in mature complex I) is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free but otherwise complete enzyme. We propose NDUFAF2 as the recruiter of the NADH dehydrogenase module during assembly of the complex. Our results provide new molecular level understanding of thendufs4-/-mouse model and complex I-linked mitochondrial disease.
Combining Magnetoencephalography with Telemetric Streaming of Intracranial Recordings and Deep Brain Stimulation – a Feasibility Study
Authors: Hnazaee Mansoureh Fahimi , Sure Matthias , O’Neill George , Leogrande Gaetano , Schnitzler Alfons , Florin Esther , Litvak Vladimir 
Published: July 2023

AbstractThe combination of subcortical Local Field Potential (LFP) recordings and stimulation with Magnetoencephalography (MEG) in Deep Brain Stimulation (DBS) patients enables the investigation of cortico-subcortical communication patterns and provides insights into DBS mechanisms. Until now, these recordings have been carried out in post-surgical patients with externalised leads. However, a new generation of telemetric stimulators makes it possible to record and stream LFP data in chronically implanted patients. Nevertheless, whether such streaming can be combined with MEG has not been tested.In the present study, we tested the most commonly implanted telemetric stimulator – Medtronic Percept PC with a phantom in three different MEG systems: two cryogenic scanners (CTF and MEGIN) and an experimental Optically Pumped Magnetometry (OPM)-based system.We found that when used in combination with the new SenSight segmented leads, Percept PC telemetric streaming only generates band-limited interference in the MEG at 123Hz and harmonics. However, the ‘legacy streaming mode’ used with older lead models generates multiple, dense artefact peaks in the physiological range of interest (below 50Hz).The effect of stimulation on MEG critically depends on whether it is done in bipolar (between two contacts on the lead) or monopolar (between a lead contact and the stimulator case) mode. Monopolar DBS creates severe interference in the MEG as previously reported. However, we found that the OPM system is more resilient to this interference and could provide artefact-free measurements at least for limited frequency ranges.A resting measurement in the MEGIN system from a Parkinson’s patient implanted with Percept PC and subthalamic SenSight leads revealed artefact patterns consistent with our phantom recordings. Moreover, analysis of LFP-MEG coherence in this patient showed oscillatory coherent networks consistent in their frequency and topography with those described in published group studies done with externalised leads.In conclusion, Percept PC telemetric streaming with SenSight leads is compatible with MEG. Furthermore, OPM sensors could provide additional new opportunities for studying DBS effects.
Bacteroidalesas a Fecal Contamination Indicator in Fresh Produce Industry: A Baseline Measurement
Authors: Wang Jiangshan , Ranjbaran Mohsen , Verma Mohit S. 
Published: July 2023

AbstractFoodborne outbreaks caused by fecal contamination of fresh produce represent a serious concern to public health and the economy. As the consumption of fresh produce increases, public health officials and organizations have pushed for improvements in food safety procedures and environmental assessments to reduce the risk of contamination. Visual inspections and the establishment of “buffer zones” between animal feeding operations and producing fields are the current best practices for environmental assessments. However, a generalized distance guideline and visual inspections may not be enough to account for all environmental risk variables. Here, we report a baseline measurement surveying the backgroundBacteroidalesconcentration, as a quantitative fecal contamination indicator, in California’s Salinas Valley. We collected a total of 1632 samples from two romaine lettuce commercial fields at the time of harvesting through two seasons in a year. TheBacteroidalesconcentration was very low (0 – 2.00 copies/cm2). Furthermore, we established a practical methodology for evaluating the risk of fecal contamination in a real-world setting, complementing the current environmental assessment practices. This method can identify site-specific risks and offer fresh produce stakeholders a more comprehensive understanding of their fields. We anticipate this work can encourage the use ofBacteroidalesin the fresh produce industry to monitor fecal contamination and prevent future foodborne outbreaks.
Conformational dynamics underlying Atypical Chemokine Receptor 3 activation
Authors: Otun Omolade , Aljamous Christelle , Nero Elise Del , Arimont-Segura Marta , Bosma Reggie , Zarzycka Barbara , Girbau Tristan , Leyrat Cédric , de Graaf Chris , Leurs Rob , Durroux Thierry , Granier Sebastien , Cong Xiaojing , Bechara Cherine 
Published: July 2023

AbstractAtypical Chemokine Receptor 3 (ACKR3) is a G protein-coupled receptor that does not signal through G proteins. It is known as a chemokine scavenger involved in various pathologies, making it an appealing yet intriguing therapeutic target. Indeed, the structural properties that govern ACKR3 functional selectivity and the overall conformational dynamics of ACKR3 activation are poorly understood. Here we combined Hydrogen/Deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics simulations to examine the binding mode and mechanism of action of various small-molecule ACKR3 ligands of different efficacy for β-arrestin recruitment. Our results show that activation or inhibition of ACKR3 is largely governed by intracellular conformational changes of helix 6, intracellular loop 2 and helix 7, while the DRY motif becomes protected during both processes. Moreover, HDX-MS identifies the binding sites and the allosteric modulation of ACKR3 upon β-arrestin 1 binding. In summary, this study highlights the structure-function relationship of small-molecule ligands, the overall activation dynamics of ACKR3, the binding mode of β-arrestin 1 and the atypical dynamic features in ACKR3 that may contribute to its inability to activate G proteins.
S100A11 promotes focal adhesion disassembly via myosin II-driven contractility and Piezo1-mediated Ca2+entry
Authors: Mohammed Tareg Omer , Lin You-Rong , Weissenbruch Kai , Ngo Kien Xuan , Zhang Yanjun , Kodera Noriyuki , Bastmeyer Martin , Miyanari Yusuke , Taoka Azuma , Franz Clemens M. 
Published: July 2023

AbstractS100A11 is a small Ca2+-activatable protein with an established role in different cellular processes involving actin cytoskeleton remodeling, such as cell migration, membrane protrusion formation, and plasma membrane repair. It also displays Ca2+-dependent F-actin binding activity and localizes to actin stress fibers (SFs), but its precise role in regulating these structures remains unclear. Analyzing endogenous S100A11 localization in HeLa and U2OS osteosarcoma cells confirmed SF association but in addition revealed steady localization to stable focal adhesions (FAs), typically at the end of dorsal stress fibers. In contrast, S100A11 levels at FAs increased sharply, but transiently, at the onset of peripheral FA disassembly. Elevating intracellular Ca2+levels using the Ca2+ionophore ionomycin reliably stimulated both S100A11 recruitment and subsequent FA disassembly. However, pre-incubation with the non-muscle myosin II (NM II) inhibitor blebbistatin, or with an inhibitor to the stretch-activatable Ca2+channel Piezo1 effectively suppressed S100A11 recruitment, implicating S100A11 in an actomyosin contractility-driven FA disassembly mechanism involving Piezo1-dependent Ca2+influx. Applying external mechanical forces on peripheral FAs via a micropipette likewise recruited S100A11 to FAs, even when NM II was inhibited by blebbistatin or in NM IIA knockout cells, corroborating the mechanosensitive recruitment mechanism of S100A11. However, extracellular Ca2+and Piezo1 function was still indispensable, indicating that NM II-dependent contraction forces act upstream of Piezo1-mediated Ca2+influx, in turn leading to S100A11 activation and FA recruitment. Moreover, S100A11 knockout cells feature enlarged FAs and display delayed FA disassembly during cell membrane retraction, consistent with impaired FA turnover in these cells. Our results thus demonstrate a novel mechano-sensitive function for S100A11 in promoting actomyosin contractility-driven FA disassembly.