bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Modulators of Cellular Responses by Heterogeneity-sequencing
Authors: Berg Kevin , Sakellaridi Lygeri , Rummel Teresa , Hennig Thomas , Whisnant Adam , Lodha Manivel , Krammer Tobias , Prusty Bhupesh K , Dölken Lars , Saliba Antoine-Emmanuel , Erhard Florian 
Published: October 2024

AbstractThe destructive nature of single-cell transcriptomics has hindered predicting and interpreting heterogeneous outcomes of molecular challenges. By exploiting information on the pre-perturbation state and fate of thousands of individual cells using droplet-based single cell RNA-seq with metabolic RNA labeling, we developed Heterogeneity-seq for predicting causal factors that impact on molecular outcomes. Heterogeneity-seq uncovered genes with an effect on drug treatment and novel proand antiviral host factors of cytomegalovirus infection.
Adaptive Gaze and Hand Coordination while Manipulating and Monitoring the Environment in Parallel
Authors: Fooken Jolande , Johansson Roland S. , Flanagan J. Randall 
Published: October 2024

AbstractResearch on eye-hand coordination has focused on action tasks performed in isolation. However, real world action tasks are often performed concurrently with perception tasks that compete for gaze. Here we examine how participants adapt their eye and hand movements when performing an object manipulation task—in which they repeatedly grasped a ball and inserted it into a slot—while simultaneously monitoring a text display to detect probabilistically occurring letter changes. We varied the visuomotor demands of the action task by having participants use either their fingertips or tweezers. We found that fixations allocated to the action task were exclusively directed to the ball and slot, and were more prevalent when using tweezers. The timing of ball and slot fixations were coupled in time with ball grasp and slot entry. On average, gaze shifted away from the landmarks ∼400 ms before contact when using fingertips—allowing the use of peripheral vision to direct the hand—and around the contact time when using tweezers—further allowing central vision to guide the hand as it approached the ball or slot. We found that participants controlled the timing of their hand movements, as well as the timing and patterns (sequence of fixations) of their eye movements, to exploit the temporal regularities of the perception task, thereby lowering the probability that a letter change would occur during action task fixations. Our results illustrate that eye-hand coordination can be flexibly and intelligently adapted when simultaneously acting on and perceiving the environment.
Hijacking and recording intracellular RNAs in human cells using eukaryotic reprogrammed tracrRNAs
Authors: Lee Seok-Hoon , Park Junho , Jung Chanju , Bae Sangsu 
Published: October 2024

AbstractRecording intracellular RNA expression events is critical for understanding cell states and biological processes, but no method without responsive promoters is available in mammalian cells. Here, we determined the sequence formula of eukaryotic reprogrammed tracrRNA, named euRptr, which can hijack intracellular RNAs to make a complex with CRISPR-associated tools. By leveraging the programmability of euRptr, we devised the system “CHEETAH” to directly capture and record intracellular RNAs in human cells. We validated that CHEETAH induces self-editing by hijacking endogenous mRNAs, that CHEETAH selectively records different viral RNA fragments on a DNA reporter using base editors with a shared-euRptr, and that CHEETAH enables multiplexed, time-resolved recording of viral RNAs on a DNA Tape using prime editors, providing a new avenue for investigating intracellular RNA in eukaryotes.
Exploring N6-Methyladenosine and long transcripts in glioma cells and extracellular vesicles
Authors: Batool Syeda Maheen , Escobedo Ana K. , Lee Hanna , Khanna Prerna , Haas Kase D. , Hsia Tiffaney , Carter Bob S. , Balaj Leonora 
Published: October 2024

AbstractGlioma represents the most common primary central nervous system (CNS) neoplasm in adults. Previous studies have identified m6A as a key player in glioma pathogenesis, promoting cell stemness and tumor cell proliferation. However, there is also evidence of a potential anti-cancer role of m6A. Here, we present a comprehensive overview of the m6A landscape in a glioma cell line model using Nanopore direct RNA sequencing platform. The study investigates functional and biological impact of targeted knockdown (KD) of key m6A regulators (reader: IGF2BP2, writer: METTL3, eraser: ALKBH5). Transcriptome wide mapping of m6A demonstrated enrichment in CDS and 3’UTR regions. Differential patterns of non-DRACH motifs were observed across the KD conditions. Our analysis identified 716 common m6A sites across all conditions and clusters of KD specific modifications enriched for distinct functional pathways. IGF2BP2 KD was associated with pathways involving protein metabolism and apoptosis regulation. METTL3 KD was linked to cell cycle and stress response regulation and ALKBH5 KD impacted ribosome biogenesis and protein synthesis. Here, for the first time we also report detection of full-length RNA transcripts in extracellular vesicles (EVs) derived RNA from knockdown and control conditions. These findings underscore the unique contributions of each m6A regulator to glioma cell transcriptomics and suggest potential pathways for elucidating the overall role of m6A machinery in glioma pathogenesis. Important clinical applications include identification of novel diagnostic, prognostic, and therapeutic m6A RNA biomarkers.
Genomic Analysis of Progenitors in Viral Infection Implicates Glucocorticoids as Suppressors of Plasmacytoid Dendritic Cell Generation
Authors: Jo Yeara , Greene Trever T. , Zhang Kai , Chiale Carolina , Fang Ziyan , Dallari Simone , Marooki Nuha , Wang Wei , Zuniga Elina I. 
Published: October 2024

AbstractPlasmacytoid Dendritic cells (pDCs) are the most potent producers of interferons, which are critical antiviral cytokines. pDC development is, however, compromised following a viral infection, and this phenomenon, as well as its relationship to conventional (c)DC development is still incompletely understood. By using lymphocytic choriomeningitis virus (LCMV) infection in mice as a model system, we observed that DC progenitors skewed away from pDC and towards cDC development duringin vivoviral infection. Subsequent characterization of the transcriptional and epigenetic landscape of fms-like tyrosine kinase 3+(Flt3+) DC progenitors and follow-up studies revealed increased apoptosis and reduced proliferation in different individual DC-progenitors as well as a profound IFN-I-dependent ablation of pre-pDCs, but not pre-DC precursor, after both acute and chronic LCMV infections. In addition, integrated genomic analysis identified altered activity of 34 transcription factors in Flt3+DC progenitors from infected mice, including two regulators of Glucocorticoid (GC) responses. Subsequent studies demonstrated that addition of GCs to DC progenitors led to downregulated pDC-primed-genes while upregulating cDC-primed-genes, and that endogenous GCs selectively decreased pDC, but not cDC, numbers uponin-vivoLCMV infection. These findings demonstrate a significant ablation of pre-pDCs in infected mice and identify GCs as suppressors of pDC generation from early progenitors. This provides an explanation for the impaired pDC development following viral infection and links pDC generation to the hypothalamic-pituitary-adrenal axis.Significance StatementPlasmacytoid dendritic cells (pDCs) play critical roles in antiviral responses. However, adaptations of DC progenitors lead to compromised pDC generation after viral infection. Here, we characterized the transcriptional and epigenetic landscapes of DC progenitors after infection. We observed widespread changes in gene expression and chromatin accessibility, reflecting shifts in proliferation, apoptosis, and differentiation potential into various DC subsets. Notably, we identified alterations in the predicted activity of 34 transcription factors, including two regulators of glucocorticoid responses. Our data demonstrate that glucocorticoids inhibit pDC generation by reprogramming DC progenitors. These findings establish a molecular framework for understanding how DC progenitors adapt to infection and highlight the role of glucocorticoid signaling in this process.
Immune cell death on silicone surfaces drives biofilm formation
Authors: Jagirdar Sameer Kumar , Jhunjhunwala Siddharth 
Published: October 2024

AbstractSilicone venous catheters are one of the most used healthcare devices worldwide. Nevertheless, they are associated with a high risk of infections, largely due to biofilm formation on catheter surfaces. Silicone is not inherently prone to bacterial adhesion; therefore, it is unclear as to what drives catheter infection and consequent biofilm formation. Previously it has been shown that circulating immune cells, including neutrophils and monocytes may adhere onto and die by apoptosis on silicone surfaces. This study investigates how immune cell death on silicone surfaces contributes to bacterial biofilm formation. The results show that neutrophil apoptosis on silicone surfaces significantly increases biofilm formation. Also, components of dead neutrophils were sufficient to cause increased biofilm formation. Further, silicone surfaces modified with a hyaluronic acid/polyarginine (HA/PA) coating reduce immune cell attachment and consequently biofilm formation. These findings suggest that to prevent catheter infection and biofilm formation, in addition to preventing bacterial attachment, it is necessary to minimize immune cell death on the catheter surface.
Integrating Multidimensional Data Analytics for Precision Diagnosis of Chronic Low Back Pain
Authors: Vickery Sam , Junker Frederick , Döding Rebekka , Belavy Daniel L , Angelova Maia , Karmakar Chandan , Becker Luis , Taheri Nima , Pumberger Matthias , Reitmaier Sandra , Schmidt Hendrik 
Published: October 2024

AbstractLow back pain (LBP) is a leading cause of disability worldwide, with up to 25% of cases become chronic (cLBP). Optimal diagnostic tools for cLBP remains unclear. Here we leveraged a comprehensive multi-dimensional data-set and machine learning-based variable importance selection to identify the most effective diagnostic tools for cLBP patient stratification. The dataset included questionnaire data, clinical and functional assessments, and spino-pelvic magnetic resonance imaging (MRI), encompassing a total of 144 parameters from 1,161 adults with (n=512) and without cLBP (n=649). Boruta and random forest were utilised for variable importance selection and cLBP classification respectively. Boruta variable selection led to pronounced variable reduction (median of all 15 datasets: 63.3%), while performing comparable to using all variables across all modality datasets. Boruta selected key variables from questionnaire, clinical, and MRI data were the most effective in distinguishing cLBP patients from controls. The most robust variables (n=9) across the whole dataset identified were psychosocial factors, neck and hip mobility, as well as lower lumbar disc herniation and degeneration. These critical variables outperformed all parameters in an unseen holdout dataset, demonstrating superior patient delineation. Paving the way for targeted diagnosis and personalized treatment strategies, ultimately enhancing clinical outcomes for cLBP patients.
The novel CFAbd-Score.kid©reveals a significant decline of abdominal symptoms in children with Cystic fibrosis aged 6 through 11 years on Elexacaftor/Tezacaftor/Ivacaftor – first results
Authors: Mainz Jochen G. , Sadrieh Pauline , Bechinger Lilith , Duckstein Franziska , Barucha Anton , Polte Louise , Naehrlich Lutz , Eickmeier Olaf , van Dullemen Suzanne , Graepler-Mainka Ute , Zagoya Carlos 
Published: October 2024

AbstractBackgroundRecently, elexacaftor/tezacaftor/ivacaftor (ETI), the turning point in the course of Cystic fibrosis (CF), was also approved for children with CF (cwCF) aged 6-11years carrying at least one F508del-mutation. Modulating the causative deficiency in the CF transmembrane conductance regulator channel was found to substantially improve the crucially affected respiratory and digestive CF-manifestations. In this regard, for people with CF aged ≥12years, we previously found that ETI decreases significantly abdominal symptoms (AS) using the CFAbd-Score©.AimsAssessing changes in AS after ETI initiation in cwCF aged 6-11years with the novel pediatric Patient-Reported Outcome Measure CFAbd-Score.kid©.MethodsThe CFAbd-Score.kid©, specially developed for cwCF aged <12years, implements pictograms, easy language and children-oriented response strategies, comprising 29 CF-specific gastrointestinal items from five domains. Its scoring algorithm developed following FDA guidelines weights items and domains differently, reaching a maximum of 100 points. CwCF completing at least one questionnaire before ETI initiation and another one during ETI therapy were included.ResultsIn four German CF centers, a total of n=52 cwCF (mean age 8.3±2.2years) were included, completing a total of n=293 questionnaires. During ETI therapy, significant decreases were observed for mean total CFAbd-Score.kid©(−31%/p<0.0001) as well as for mean sub-scores of “pain” (−26%/p<0.01), “QoL impairment” (−48%/p<0.01), “disorders of bowel movement” (−32%/p≤0.0001) and “disorders of appetite” (−42%/p<0.05).ConclusionAmong cwCF aged 6-11years, AS captured with the novel CFAbd-Score.kid©significantly decreased during the novel ETI treatment. Simultaneously, CFAbd-Score.kid©proved to be sensitive to ETI-induced changes in AS. Further validation steps and international implementation are currently in progress.
Mapping Visual Contrast Sensitivity and Vision Loss Across the Visual Field with Model-Based fMRI
Authors: Chow-Wing-Bom Hugo T. , Lisi Matteo , Benson Noah C. , Lygo-Frett Freya , Yu-Wai-Man Patrick , Dick Frederic , Maimon-Mor Roni O. , Dekker Tessa M. 
Published: October 2024

AbstractPeripheral vision is crucial for daily activities and quality of life, yet traditional measures of visual function like visual acuity primarily assess central vision. Visual field tests can evaluate peripheral vision but require extended focus combined with precise fixation, often very challenging for patients with severe sight loss. Functional MRI (fMRI) with population receptive field (pRF) mapping offers a non-invasive way to map scotomas but is limited by its reliance on single contrast levels and the necessity of accurate fixation.We developed an fMRI-based approach to measure contrast sensitivity across the visual field without the need for precise fixation. By combining large-field stimulation with varying spatial frequencies and contrast levels with either pRF mapping or a retinotopic atlas based on anatomical landmarks, we modeled contrast sensitivity in the primary visual cortex (V1) over a large (40 deg) expanse of the visual field. In seven normal-sighted participants, we characterized differences in V1 cortical sensitivity across eccentricities and visual quadrants, finding reliable and reproducible patterns of sensitivity differences at individual and session levels. Additionally, our method effectively visualized cases of simulated and disease-linked sensitivity loss at the cortical level. Crucially, we demonstrated that these results could be largely recovered using a structure-based retinotopic atlas, eliminating the need for pRF mapping and precise fixation - although such an approach reduced sensitivity.This approach, integrating large-field stimulation with a retinotopic atlas, offers a promising tool for monitoring vision loss and recovery in patients with various visual impairments, addressing a significant challenge in current clinical assessments.
Medium-dose irradiation impairs long-term hematopoietic stem cell functionality and hematopoietic recovery to cytotoxic stress
Authors: Zhang Qinyu , Rydström Anna , Hidalgo Isabel , Cammenga Jörg , Nilsson Alexandra Rundberg 
Published: October 2024

SummaryIrradiation and 5-fluorouracil (5-FU) are widely utilized tools in hematopoietic research to generate myeloablation and assess blood recovery dynamics. A comprehensive understanding of their effects on the hematopoietic system is essential for optimizing therapeutic strategies, refining experimental models to modulate hematotoxicity, and interpreting research outcomes. Despite their widespread application, the long-term hematopoietic impacts of irradiation and 5-FU, particularly on hematopoietic stem cells (HSCs), remain incompletely characterized. In this study, we therefore examined the long-term effects of 2 Gy medium-dose ionizing radiation (MDIR) and 150 mg/kg 5-FU on HSCs and the hematopoietic system’s resilience to subsequent cytotoxic stress in mice. Our findings demonstrate that MDIR, but not 5-FU, induces sustained impairments in HSC function and results in the selective depletion of MHC class II−HSCs – a subset characterized by high self-renewal potential. Furthermore, MDIR significantly compromised hematopoietic recovery following a subsequent 5-FU challenge, as evidenced by notably reduced platelet and red blood cell (RBC) counts during the critical recovery phase. These findings highlight the distinct and persistent impacts of MDIR and 5-FU on HSCs and hematopoietic function, revealing crucial differences in their mechanisms of action and long-term consequences on the hematopoietic system.
Slit regulates compartment-specific targeting of dendrites and axons in theDrosophilabrain
Authors: Deng Xiaobing , Sandoval Isaac Cervantes , Zhu Sijun 
Published: October 2024

AbstractProper functioning of the nervous system requires precise neuronal connections at subcellular domains, which can be achieved by projection of axons or dendrites to subcellular domains of target neurons. Here we studied subcellular-specific targeting of dendrites and axons in theDrosophilamushroom body (MB), where mushroom body output neurons (MBONs) and local dopaminergic neurons (DAN) project their dendrites and axons, respectively, to specific compartments of MB axons. Through genetic ablation, we demonstrate that compartment-specific targeting of MBON dendrites and DAN axons involves mutual repulsion of MBON dendrites and/or DAN axons between neighboring compartments. We further show that Slit expressed in subset of DANs mediates such repulsion by acting through different Robo receptors in different neurons. Loss of Slit-mediated repulsion leads to projection of MBON dendrites and DAN axons into neighboring compartments, resulting formation of ectopic synaptic contacts between MBONs and DANs and changes in olfactory-associative learning. Together, our findings suggest that Slit-mediated repulsion controls compartment-specific targeting of MBON dendrites and DAN axons, which ensures precise connections between MBON dendrites and DAN axons and proper learning and memory formation.
Structure elucidation, biosynthetic gene cluster distribution, and biological activities of ketomemicin analogs inSalinispora
Authors: Castro-Falcón Gabriel , Guillén-Matus Dulce G. , Da Silva Elany Barbosa , Guo Wentao , Ross Alicia , Magalhães Serafim Mateus Sá , Maciel Fernandes Thais Helena , Tantillo Dean J. , O’Donoghue Anthony J. , Jensen Paul R. 
Published: October 2024

ABSTRACTWe report three new ketomemicin pseudopeptides (1–3) from extracts of the marine actinomyceteSalinispora pacificastrain CNY-498. Their constitution and relative configuration were elucidated using NMR, mass spectrometry, and quantum chemical calculations. Using GNPS molecular networking and publicly availableSalinisporaLCMS datasets, five additional ketomemicin analogs (4–8) were identified with ketomemicin production detected broadly acrossSalinisporaspecies. The ketomemicin biosynthetic gene cluster (ktm) is highly conserved inSalinispora, occurring in 79 of 118 public genome sequences including eight of the nine named species. OutsideSalinispora, ktmhomologs were detected in various genera of the phylum Actinomycetota that might encode novel ketomemicin analogs. Ketomemicins1–3were tested against a panel of eleven proteases, with2displaying moderate inhibitory activity. This study describes the first report of ketomemicin production bySalinisporacultures, the distribution of the corresponding biosynthetic gene cluster, and the protease inhibitory activity of new ketomemicin derivatives.Table of Content/Graphical Abstract
BT-11 repurposing potential for Alzheimer’s disease and insights into its mode of actions
Authors: Birnbaum Emily M. , Xie Lei , Serrano Peter , Rockwell Patricia , Figueiredo-Pereira Maria E. 
Published: October 2024

AbstractNeuroinflammation is a key pathological hallmark of Alzheimer’s disease (AD). Investigational and FDA approved drugs targeting inflammation already exist, thus drug repurposing for AD is a suitable approach. BT-11 is an investigational drug that reduces inflammation in the gut and improves cognitive function. BT-11 is orally active and binds to lanthionine synthetase C-like 2 (LANCL2), a glutathione-s-transferase, thus potentially reducing oxidative stress. We investigated the effects of BT-11 long-term treatment on the TgF344-AD rat model. BT-11 reduced hippocampal-dependent spatial memory deficits, Aβ plaque load and neuronal loss in males, and mitigated microglia numbers in females. BT-11 treatment led to hippocampal transcriptomic changes in signaling receptor, including G-protein coupled receptor pathways. We detected LANCL2 in hippocampal nuclear and cytoplasmic fractions with potential different post-translational modifications, suggesting distinct functions based on its subcellular localization. LANCL2 was present in oligodendrocytes, showing a role in oligodendrocyte function. To our knowledge, these last two findings have not been reported. Overall, our data suggest that targeting LANCL2 with BT-11 improves cognition and reduces AD-like pathology by potentially modulating G-protein signaling and oligodendrocyte function. Our studies contribute to the field of novel immunomodulatory AD therapeutics, and merit further research on the role of LANCL2 in this disease.