bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD83 Receptor Unveiled as a Therapeutic Target in Metastatic Breast Cancer through Single-Cell RNA-Seq
Authors: Sayad Saed , Hiatt Mark , Mustafa Hazem 
Published: January 2024

AbstractBackgroundMetastatic breast cancer is an advanced stage of the disease in which cancer cells have spread to organs beyond the breast, posing a significant clinical challenge, necessitating the development of novel therapeutic approaches. Gaining a profound understanding of the intricacies of metastasis is essential for developing effective interventions. In this study, we investigated the CD83 gene and its receptor as a promising therapeutic target in metastatic breast cancer.MethodWe obtained single-cell transcriptomes (GSE75688) from the NIH portal website. These transcriptomes encompassed samples from eleven patients (BC01-BC11), which included two lymph node metastases (BC03LN, BC07LN). Our analysis focused on identifying genes with distinct expression patterns between metastatic and primary single cells.ResultsIn the array of 22 tables (comprising two metastatic and eleven primary tables) featuring the top 800 differentially expressed genes in each, CD83 stood out as the sole significantly upregulated gene consistently shared across all eleven patients at the intersection. CD83 is a protein that plays a crucial role in the immune system, particularly in the context of antigen presentation, immune regulation and immune checkpoint, suggesting its potential involvement in breast cancer progression and metastasis. Based on these findings, we hypothesized that blocking the CD83 receptor on the cell membrane using an antibody could effectively inhibit cell growth in metastatic breast cancer.ConclusionWe propose a novel therapeutic approach by targeting the CD83 receptor on the cell membrane to inhibit cell growth and metastasis in breast cancer. While these findings are promising, further research is needed to validate the efficacy and safety of CD83-targeted therapies. If successful, such treatments could offer improved options for patients with metastatic breast cancer, addressing a critical need for more effective interventions in advanced stages of the disease.
Cluster effect through the oligomerisation of bioactive disaccharide AMOR on pollen tube capacitation inTorenia fournieri
Authors: Mizukami Akane G , Kusano Shuhei , Hagihara Shinya , Higashiyama Tetsuya 
Published: January 2024

ABSTRACRTArabinogalactan proteins (AGPs) are plant-specific glycoproteins involved in cellular mechanics and signal transduction. There has been major progress in understanding the structure, synthesis, and molecular functions of their carbohydrate chains; however, the mechanisms by which they function as signalling molecules remain unclear. Here, methyl-glucuronosyl arabinogalactan (AMOR; Me-GlcA-β(1,6)-Gal), a disaccharide structure at the end of AGP carbohydrate chains, was oligomerised via chemical synthesis. The biological activity of AMOR oligomers was enhanced via clustering of the carbohydrate chains. Furthermore, AMOR oligomers yielded a pollen tube morphology (i.e., callose plug formation) similar to that when cultured with native AMOR, suggesting it may be functionally similar to native AMOR.
tRNA expression and modification landscapes, and their dynamics during zebrafish embryo development
Authors: Rappol Tom , Waldl Maria , Chugunova Anastasia , Hofacker Ivo L. , Pauli Andrea , Vilardo Elisa 
Published: January 2024

ABSTRACTtRNA genes exist in multiple copies in the genome of all organisms across the three domains of life. Besides the sequence differences across tRNA copies, extensive post-transcriptional modification adds a further layer to tRNA diversification. Whilst the crucial role of tRNAs as adapter molecules in protein translation is well established, whether all tRNA are actually expressed, and whether the differences across isodecoders play any regulatory role is only recently being uncovered. Here we built upon recent developments in the use of NGS-based methods for RNA modification detection and developed tRAM-seq, an experimental protocol andin silicoanalysis pipeline to investigate tRNA expression and modification. Using tRAM-seq we analysed the full ensemble of nucleo-cytoplasmic and mitochondrial tRNAs during embryonic development of the model vertebrate zebrafish. We show that the repertoire of tRNAs changes during development, with an apparent major switch in tRNA isodecoder expression and modification profile taking place around the start of gastrulation. Taken together, our findings suggest the existence of a general reprogramming of the expressed tRNA pool, possibly gearing the translational machinery for distinct stages of the delicate and crucial process of embryo development.
Fluorinated trehalose analogues for cell surface engineering and imaging ofMycobacterium tuberculosis
Authors: Guy Collette S. , Gott James A. , Ramírez-Cárdenas Jonathan , de Wolf Christopher , Furze Christopher M. , West Geoff , Muñoz-García Juan C. , Angulo Jesus , Fullam Elizabeth 
Published: January 2024

AbstractThe sensitive, rapid and accurate diagnosis ofMycobacterium tuberculosis(Mtb) infection is a central challenge in controlling the global tuberculosis (TB) pandemic. Yet the detection of mycobacteria is often made difficult by the low sensitivity of current diagnostic tools, with over 3.6 million TB cases missed each year. To overcome these limitations there is an urgent need for next-generation TB diagnostic technologies. Here we report the use of a discrete panel of native19F-trehalose (F-Tre) analogues to label and directly visualiseMtbby exploiting the uptake of fluorine-modified trehalose analoguesviathe mycobacterial trehalose LpqY-SugABC ATP-binding cassette (ABC) importer. We discovered the extent of modified F-Tre uptake correlates with LpqY substrate recognition and characterisation of the interacting sites by saturation transfer difference NMR coupled with molecular dynamics provides a unique glimpse into the molecular basis of fluorine-modified trehalose import inMtb. Lipid profiling demonstrated that F-Tre analogues modified at positions 2, 3 and 6 are incorporated into mycobacterial cell-surface trehalose-containing glycolipids. This rapid one-step labelling approach facilitates the direct visualisation of F-Tre-labelledMtbby focused ion beam (FIB) secondary ion mass spectrometry (SIMS), enabling pathogen specific detection. Collectively, our findings highlight that F-Tre analogues have potential as tools to probe and unravelMtbbiology and can be exploited to detect and image TB.
LSD Modulates Proteins Involved in Cell Proteostasis, Energy Metabolism and Neuroplasticity in Human Cerebral Organoids
Authors: Costa Marcelo N. , Goto-Silva Livia , Nascimento Juliana M. , Domith Ivan , Karmirian Karina , Feilding Amanda , Trindade Pablo , Martins-de-Souza Daniel , Rehen Stevens K. 
Published: January 2024

ABSTRACTProteomic analysis of human cerebral organoids may reveal how psychedelics regulate biological processes, shedding light on drug-induced changes in the brain. This study elucidates the proteomic alterations induced by lysergic acid diethylamide (LSD) in human cerebral organoids. By employing high-resolution mass spectrometry-based proteomics, we quantitatively analyzed the differential abundance of proteins in cerebral organoids exposed to LSD. Our findings indicate changes in proteostasis, energy metabolism, and neuroplasticity-related pathways. Specifically, LSD exposure led to alterations in protein synthesis, folding, autophagy, and proteasomal degradation, suggesting a complex interplay in the regulation of neural cell function. Additionally, we observed modulation in glycolysis and oxidative phosphorylation, crucial for cellular energy management and synaptic function. In support of the proteomic data, complementary experiments demonstrated LSD’s potential to enhance neurite outgrowth in vitro, confirming its impact on neuroplasticity. Collectively, our results provide a comprehensive insight into the molecular mechanisms through which LSD may affect neuroplasticity and potentially contribute to therapeutic effects for neuropsychiatric disorders.
Decreased Left Atrial Cardiomyocyte FGF13 Expression Increases Vulnerability to Postoperative Atrial Fibrillation in Humans
Authors: Fischer Matthew A. , Arrieta Adrian , Angelini Marina , Soehalim Elizabeth , Chapski Douglas J. , Shemin Richard J. , Vondriska Thomas M. , Olcese Riccardo 
Published: January 2024

AbstractPostoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and a significant cause of increased morbidity and mortality. The development of novel POAF therapeutics has been limited by an insufficient understanding of molecular mechanisms promoting atrial fibrillation. In this observational cohort study, we enrolled 28 patients without a history of atrial fibrillation that underwent mitral valve surgery for degenerative mitral regurgitation and obtained left atrial tissue samples along the standard atriotomy incision in proximity to the right pulmonary veins. We isolated cardiomyocytes and performed transcriptome analyses demonstrating 13 differentially expressed genes associated with new-onset POAF. Notably, decreased expression of fibroblast growth factor 13 (FGF13), a fibroblast growth factor homologous factor known to modulate voltage-gated sodium channel NaV1.5 inactivation, had the most significant association with POAF. To assess the functional significance of decreased FGF13 expression in atrial myocytes, we performed patch clamp experiments on neonatal rat atrial myocytes after siRNA-mediated FGF13 knockdown, demonstrating action potential prolongation. These critical findings indicate that decreased FGF13 expression promotes vulnerability to POAF.
PREFRONTAL CORRELATES OF FEAR GENERALIZATION DURING ENDOCANNABINOID DEPLETION
Authors: Rosas-Vidal Luis E. , Naskar Saptarnab , Mayo Leah M. , Perini Irene , Altemus Megan , Engelbrektsson Hilda , Jagasia Puja , Heilig Markus , Patel Sachin 
Published: January 2024

AbstractMaladaptive fear generalization is one of the hallmarks of trauma-related disorders. The endocannabinoid 2-arachidonoylglycerol (2-AG) is crucial for modulating anxiety, fear, and stress adaptation but its role in balancing fear discrimination versus generalization is not known. To address this, we used a combination of plasma endocannabinoid measurement and neuroimaging from a childhood maltreatment exposed and non-exposed mixed population combined with human and rodent fear conditioning models. Here we show that 2-AG levels are inversely associated with fear generalization at the behavioral level in both mice and humans. In mice, 2-AG depletion increases the proportion of neurons, and the similarity between neuronal representations, of threat-predictive and neutral stimuli within prelimbic prefrontal cortex ensembles. In humans, increased dorsolateral prefrontal cortical-amygdala resting state connectivity is inversely correlated with fear generalization. These data provide convergent cross-species evidence that 2-AG is a key regulator of fear generalization and suggest 2-AG deficiency could represent a trauma-related disorder susceptibility endophenotype.
Synthesis and application of a photocaged L-lactate
Authors: Miyazaki Ikumi , Tsao Kelvin K. , Kamijo Yuki , Nasu Yusuke , Terai Takuya , Campbell Robert E. 
Published: January 2024

Abstractl-Lactate, once considered a metabolic waste product of glycolysis, is now recognized as a vitally important metabolite and signaling molecule in multiple biological pathways. However, exploringl-lactate’s emerging intra- and extra-cellular roles is hindered by a lack of tools to locally perturbl-lactate concentration intracellularly and extracellularly. Photocaged compounds are a powerful way to introduce bioactive molecules with spatial and temporal precision using illumination. Here, we report the development of a photocaged derivative ofl-lactate, 4-methoxy-7-nitroindolinyll-lactate (MNI-l-lac), that releasesl-lactate upon UV illumination. We validated MNI-l-lac in cell culture by demonstrating that the photorelease ofl-lactate elicits a response from genetically encoded extra- and intracellularl-lactate biosensors. These results indicate that MNI-l-lac may be useful for perturbing the concentration of endogenousl-lactate in order to investigatel-lactate’s roles in metabolism and signaling pathways.
Proteasome-dependent Orc6 removal from chromatin upon S-phase entry safeguards against MCM reloading and tetraploidy
Authors: Hayashi-Takanaka Yoko , Hiratani Ichiro , Haraguchi Tokuko , Hiraoka Yasushi 
Published: January 2024

AbstractDNA replication is tightly regulated to occur only once per cell cycle, as untimely re-initiation can lead to aneuploidy, which is associated with early senescence and cancer. The pre-replication complex (comprising Orc1-6, Cdc6, Cdt1, and MCM) is essential for the initiation of DNA replication, but the dynamics and function of Orc6 during the cell cycle remain elusive. Here, we demonstrate that Orc6 associates with chromatin during G1-phase and dissociates upon S-phase entry. The dissociation of Orc6 from chromatin is dependent on proteasome activity, and inhibition of the proteasome leads to the accumulation of chromatin-bound Orc6, which promotes abnormal MCM loading after S-phase entry without undergoing mitosis in human immortalized hTERT-RPE1 cells. Following release from proteasome inhibition, cells with elevated levels of chromatin-bound Orc6 and MCM proceed to the next replication phase as tetraploid cells. Our findings suggest that the proteasome-dependent dissociation of Orc6 after DNA replication is critical for preventing inappropriate MCM reloading and tetraploid formation.
Systemic inflammation accelerates neurodegeneration in a rat model of Parkinson’s disease overexpressing human alpha synuclein
Authors: Massaro Cenere Mariangela , Tiberi Marta , Paldino Emanuela , D’Addario Sebastian Luca , Federici Mauro , Giacomet Cecilia , Cutuli Debora , Matteocci Alessandro , Cossa Francesca , Zarrilli Beatrice , Casadei Nicolas , Ledonne Ada , Petrosini Laura , Berretta Nicola , Fusco Francesca Romana , Chiurchiù Valerio , Mercuri Nicola B. 
Published: January 2024

ABSTRACTIncreasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson’s disease (PD). In the present study, we assessed the development of symptoms on a genetic PD rat model that overexpresses human α-synuclein (Snca+/+) at a presymptomatic age, exposed to a pro-inflammatory insult by intraperitoneal injection of lipopolysaccharide (LPS), using immunohistology, high-dimensional flow cytometry, constant potential amperometry, and behavioral analyses. A single injection of LPS into WT andSnca+/+rats triggered long-lasting increase in the activation of pro-inflammatory microglial markers, monocytes, and T lymphocytes. However, only LPSSnca+/+rats showed dopaminergic neuronal loss in thesubstantia nigra pars compacta(SNpc), associated with a reduction in the release of evoked dopamine in the striatum. No significant changes were observed in the behavioral domain.We propose our double-hit animal as a reliable model to investigate the mechanisms whereby α-synuclein and inflammation interact to promote neurodegeneration in PD.
Gene-specific RNA homeostasis revealed by perturbation of coactivator complexes
Authors: Forouzanfar Faezeh , Plassard Damien , Furst Audrey , Moreno David F. , Oliveira Karen A. , Reina-San-Martin Bernardo , Tora László , Molina Nacho , Mendoza Manuel 
Published: January 2024

SummaryTranscript buffering entails the reciprocal modulation of mRNA synthesis and degradation rates to maintain stable RNA levels under varying cellular conditions. Current research supports a global, non-sequence-specific connection between mRNA synthesis and degradation, but the underlying mechanisms are still unclear. In this study, we investigated changes in RNA metabolism following acute depletion of TIP60/KAT5, the acetyltransferase subunit of the NuA4 transcriptional coactivator complex, in mouse embryonic stem cells. By combining RNA sequencing of nuclear, cytoplasmic, and newly synthesised transcript fractions with biophysical modelling, we demonstrate that TIP60 predominantly enhances transcription of numerous genes, while a smaller set of genes undergoes TIP60-dependent transcriptional repression. Surprisingly, transcription changes caused by TIP60 depletion were offset by corresponding changes in RNA nuclear export and cytoplasmic stability, indicating gene-specific buffering mechanisms. Similarly, disruption of the unrelated ATAC coactivator complex also resulted in gene-specific transcript buffering. These findings reveal that transcript buffering functions at a gene-specific level and suggest that cells dynamically adjust RNA splicing, export, and degradation in response to individual RNA synthesis alterations, thereby sustaining cellular homeostasis.
Tapeworm infection affects sleep behavior in three-spined stickleback
Authors: Bauhus Marc , Mews Sina , Kurtz Joachim , Brinker Alexander , Peuß Robert , Anaya-Rojas Jaime 
Published: January 2024

AbstractSleep is a highly complex and conserved biological process that affects several body functions and behaviors. Recent evidence suggests that there is a reciprocal interaction between sleep and immunity. For instance, fragmented sleep can increase the probability of parasitic infections and reduce the ability of infected hosts to fight infections. It is also known, particularly in humans and other mammals, that viral and bacterial infections alter the sleep patterns of infected individuals. However, the effects of macro-parasitic infections on sleep remain largely unknown. In this study, we investigated whether macro-parasite infections could alter the sleep of their hosts. We experimentally infected three-spined sticklebacks (Gasterosteus aculeatus) with the tapewormSchistocephalus solidusand used a hidden Markov model to characterize sleep-associated behaviors in the sticklebacks. At an early time-point, 1-4 days after parasite exposure, infected fish showed no difference in sleep compared with non-exposed fish, whereas fish that were exposed but could fend off the infection slept less during the daytime. At a later time-point, 29-32 days after exposure, infected fish slept more than uninfected fish, while exposed-but-not-infected fish slept less than non-exposed fish. Using RNA-seq of brain tissue, we identified several immune- and sleep-associated genes that potentially underlie the observed behavioral changes. These results provide the first insight into the complex association between macro-parasite infection, immunity, and sleep in fish and may thus contribute to a better understanding of the reciprocal interaction between sleep and immunity.
A feather star is born: embryonic development and nervous system organization in the crinoidAntedon mediterranea
Authors: Mercurio S. , Gattoni G. , Scarì G. , Ascagni M. , Barzaghi B. , Elphick M. R. , Benito-Gutiérrez E. , Pennati R. 
Published: January 2024

AbstractBackgroundCrinoids belong to the phylum Echinodermata, marine invertebrates with a highly derived pentaradial body plan. As the only living members of the Pelmatozoa, the sister group to other extant echinoderms, crinoids are in a key phylogenetic position to reconstruct the evolutionary history of this phylum. However, the development of crinoids has been scarcely investigated, limiting their potential for comparative studies. Many crinoids are difficult to collect in the wild and embryo manipulation is challenging. Conversely, the Mediterranean feather starAntedon mediterraneacan be found in shallow waters and has been used for experimental studies, most notably to investigate regeneration.ResultsThe aim here was to establishA. mediterraneaas an experimental system for developmental biology. To accomplish this, we set up a method for culturing embryosin vitrofrom zygote to hatching larva stage that allowed us to define a developmental timeline and a standardized staging system for this species. We then optimized protocols to characterize the development of the main structures of the feather star body plan, using a combination of microscopy techniques and whole mount immunohistochemistry andin situhybridization chain reaction. Focusing on the nervous system, we show that the larval apical organ includes a combination of serotonergic, GABAergic and glutamatergic neurons that form under the influence of a conserved anterior molecular signature. The larval neural plexus is instead composed of glutamatergic neurons and develops during the formation of the ciliary bands. Larval neurons disappear at metamorphosis, and the ectoneural and entoneural components of the adult nervous system develop early in post-metamorphic stages. Furthermore, the oral ectoderm that contains the ectoneural system acquires an “anterior” signature expressingSix3/6andLhx2/9orthologs.ConclusionsOur results deepen our knowledge on crinoid development and provide new techniques to investigate feather star embryogenesis, promoting the use ofA. mediterraneain developmental and evolutionary biology. This in turn will pave the way for the inclusion of crinoids in comparative studies to understand the origin of the echinoderm body plan and clarify many unanswered questions on deuterostome evolution.
Multiple variants of the type VII secretion system in Gram-positive bacteria
Authors: Garrett Stephen R. , Higginson Andrew B. , Palmer Tracy 
Published: January 2024

AbstractType VII secretion systems (T7SS) are found in bacteria across the Bacillota and Actinomycetota phyla and have been well described inStaphylococcus aureus,Bacillus subtilisand pathogenic mycobacteria. The T7SS from Actinomycetota and Bacillota share two common components, a membrane-bound EccC/EssC ATPase and EsxA, a small helical hairpin protein of the WXG100 family. However, they also have additional phylum-specific components, and as a result they are termed the T7SSa (Actinomycetota) and T7SSb (Bacillota), respectively. Here we identify additional organisations of the T7SS across these two phyla and describe eight additional T7SS subtypes which we have named T7SSc – T7SSj. T7SSd is found exclusively in Actinomycetota including theOlselnellaandBifodobacteriumgenus, whereas the other seven are found only in Bacillota. All of the novel subtypes contain the canonical ATPase (TsxC) and the WXG100-family protein (TsxA). Most of them also contain a small ubiquitin-related protein, TsxB, related to the T7SSb EsaB/YukB component. Protein kinases, phosphatases and forkhead associated (FHA) proteins are often encoded in the novel T7SS gene clusters. Candidate substrates of these novel T7SS subtypes include LXG-domain and RHS proteins. Predicted substrates are frequently encoded alongside genes for additional small WXG100-related proteins that we speculate serve as co-secretion partners. Collectively our findings reveal unexpected diversity in the T7SS in Gram-positive bacteria.