bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Analysis of Antioxidant Activity, ROS, and Relative Water Content Between Red and Green Cabbage
Authors: Sojib Md. Rayhan , Methela Nusrat Jahan , Das Biswajit , Siddique Md Nure Adil , Sultana Sadia , Karim Ataul , Islam Rafiqul , Jone Md Jahid Hasan 
Published: July 2024

AbstractCabbage, the second largest leafy vegetable, is highly valued for its nutritional richness and versatility. As health consciousness increases, the worldwide demand for cabbage continues to grow steadily. Cabbages come in various forms, varying in size, color, texture, and nutritional properties. An experiment was conducted to distinguish significant differences in relative water content (RWC of leaf and RWC of head), relative oxygen species (MDA and H2O2), and antioxidant properties (POD, APX, and CAT) between red and green cabbage varieties. Cabbage samples were grown under fertilizer and control conditions to observe the impact of fertilizers on the acquisition of these properties. The results indicated that fertilizer application positively influenced the acquisition of relative water content, relative oxygen species, and antioxidant properties in both cabbage varieties. The results emphasized that red cabbage excelled in antioxidants and ROS levels, containing higher amounts compared to green cabbage. Conversely, green cabbage showed greater relative water content in both cultivation conditions. These findings suggest that consumers seeking higher antioxidant and ROS levels in their diet may benefit from incorporating more red cabbage into their meals. Further research into the mechanisms behind differences in red and green cabbage could inform breeding programs, enhancing nutritional traits for agricultural and dietary purposes.
Single field evolution rule governs the dynamics of representational drift in mouse hippocampal dorsal CA1 region
Authors: Chen Cong , Yao Shuyang , Cheng Sihui , Li Ang , Yan Yusen , Zhang Xiang , Liu Yuanjing , Wang Yumeng , Cao Qichen , Miao Chenglin 
Published: July 2024

SummaryHow the brain reconciles dynamism with stability to balance learning and reliable memory storage has not yet been fully understood. To address the critical question, we longitudinally recorded place cells in the hippocampal dorsal CA1 region over 7 to 56 days, utilizing multiple goal-oriented navigation paradigms across various environments. We found that over 80% of place cells displayed multiple fields, undergoing complex evolution events including field disappearance, formation, and retention. Place fields from the same neuron showed limited coordination (∼5%), with a preference for synchronized changes. We further uncovered the single field evolution rule: the longer a field remains active, the more likely it is to continue being active; conversely, the longer a field remains inactive, the less likely it is to recover the future fate of a place field depends on its past activity. Mathematical modeling revealed that this rule sufficiently demonstrates the growing stability of the dCA1 spatial representation at the population level.
Assessing Healthy Vaccinee Effect in COVID-19 Vaccine Effectiveness Studies: A National Cohort Study in Qatar
Authors: Chemaitelly Hiam , Ayoub Houssein H. , Coyle Peter , Tang Patrick , Hasan Mohammad R. , Yassine Hadi M. , Al Thani Asmaa A. , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed Ghaith , Al-Romaihi Hamad Eid , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto , Butt Adeel A. , Abu-Raddad Laith J. 
Published: July 2024

AbstractBackgroundThis study investigated the presence of the healthy vaccinee effect—the imbalance in health status between vaccinated and unvaccinated individuals—in two COVID-19 vaccine effectiveness studies involving primary series and booster vaccinations. It also examined the temporal patterns and variability of this effect across different subpopulations by analyzing the association between COVID-19 vaccination and non-COVID-19 mortality in Qatar.MethodsTwo matched, retrospective cohort studies assessed the incidence of non-COVID-19 death in national cohorts of individuals with a primary series vaccination versus no vaccination (two-dose analysis), and individuals with three-dose (booster) vaccination versus primary series vaccination (three-dose analysis), from January 5, 2021, to April 9, 2024.ResultsThe adjusted hazard ratio (aHR) for non-COVID-19 death was 0.76 (95% CI: 0.64-0.90) in the two-dose analysis and 0.85 (95% CI: 0.67-1.07) in the three-dose analysis. In the first six months of follow-up in the two-dose analysis, the aHR was 0.35 (95% CI: 0.27-0.46); however, the combined analysis of all subsequent periods showed an aHR of 1.52 (95% CI: 1.19-1.94). In the first six months of follow-up in the three-dose analysis, the aHR was 0.31 (95% CI: 0.20-0.50); however, the combined analysis of all subsequent periods showed an aHR of 1.37 (95% CI: 1.02-1.85). The overall effectiveness of the primary series and third-dose vaccinations against severe, critical, or fatal COVID-19 was 95.9% (95% CI: 94.0-97.1) and 34.1% (95% CI: −46.4-76.7), respectively. Subgroup analyses showed that the healthy vaccinee effect is pronounced among those aged 50 years and older and among those more clinically vulnerable to severe COVID-19.ConclusionA strong healthy vaccinee effect was observed in the first six months following vaccination. This effect may have stemmed from a lower likelihood of vaccination among seriously ill, end-of-life individuals, and less mobile elderly populations.
A retrograde transit filter mediated by optineurin controls mitostasis in distal axons
Authors: Marahori Natalia A. , Gailer Barbara , Schifferer Martina , Kleele Tatjana , Iatroudi Anna , Hannan Shabab B. , Avramopoulos Petros , Engelhardt Stefan , Lakadamyali Melike , Brill Monika S. , Misgeld Thomas 
Published: July 2024

ABSTRACTThe mechanisms of mitochondrial homeostasis in neurons—‘mitostasis’—are enigmatic and disease-prone, given a neuron’s large synaptic pool of mitochondria. To better understand mitostasis in mature mouse motor axons, we used ex vivo optical pulse-chase measurements of mitochondrial volume flux and identified a reiterative degradation system near presynaptic terminals and distal paranodes, which accounts for 75% of mitochondrial turnover in synapses. This distal filter system captures dysfunctional mitochondria from the retrograde stream and redirects them for lysosomal degradation. It depends on optineurin, a motor neuron disease-related mitophagy adaptor, but not on PINK1 and parkin, implicating a non-canonical mitophagy pathway. In presymptomatic motor neuron disease models, where retrograde transport is disrupted, the fraction of removed mitochondria is increased. Thus, we identify a new mitostasis system in distal axons with a cascade of checkpoints for local mitophagy, which normally maintains mitochondrial mass balance but is disrupted early in degenerative axonopathies.
Rapid liquid biopsy assessment through gene profiling from the kidney biopsy transport medium: a technical validation and a proof-of-concept pilot study
Authors: Li Ziyang , Welters Marij J.P. , de Vries Aiko P.J. , Bruijn Jan A. , Baelde Hans J. , Kers Jesper 
Published: July 2024

AbstractBackgroundRapid diagnosis is pivotal in kidney disease for timely and targeted treatment. Conventional microscopic and molecular assessments from biopsy tissues rely on extra sample processing (e.g., formalin-fixation, paraffin-embedding (FFPE)) or an extra biopsy core (e.g., Molecular Microscope Diagnostic System [MMDx]), making same-day diagnosis impractical. Therefore, we introduce a novel and freely accessible material, the biopsy transport medium (BTM), which can serve as a source of biomarkers with high potential and is promising for accelerating the assessment workflow.MethodsBiopsies were cut from tumor-free tissues obtained from nephrectomies to create BTM mimics for homogenization. We optimized the RNA extraction procedure from BTM by investigating crucial steps in the process. We measured the quantity and integrity of the RNA and different biomarkers derived from BTM through qPCR. Additionally, we performed gene signature profiling on BTM using the Banff Human Organ Transplant (B-HOT) panel in the NanoString nCounter platform as a proof-of-concept study.ResultsThe storage time (the duration a biopsy is stored in the BTM), ranging from 0.5 to 24 hours did not significantly affect RNA quality and yield. Differential gene expression analysis on allograft rejection BTM described specific profiles related to rejection. A significant correlation was observed between rejection-related transcripts and the corresponding Banff lesion scores.ConclusionThis study validated that the BTM can provide transcriptomic information relevant to the state of the kidney. The proof-of-concept study demonstrated that BTM has great potential for reflecting the status of the transplanted kidney. Tailored qPCR panels could allow for fast (same-day) molecular diagnosis.
12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice
Authors: Nargis Titli , Muralidharan Charanya , Enriquez Jacob R. , Wang Jiayi E. , Kaylan Kerim , Chakraborty Advaita , Pratuangtham Sarida , Figatner Kayla , Nelson Jennifer B. , May Sarah C. , Nadler Jerry L. , Boxer Matthew B. , Maloney David J. , Tersey Sarah A. , Mirmira Raghavendra G. 
Published: July 2024

ABSTRACTType 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing β cells and involves an interplay between β cells and cells of the innate and adaptive immune systems. We investigated the therapeutic potential of targeting 12-lipoxygenase (12-LOX), an enzyme implicated in inflammatory pathways in β cells and macrophages, using a mouse model in which the endogenous mouseAlox15gene is replaced by the humanALOX12gene. Our finding demonstrated that VLX-1005, a potent 12-LOX inhibitor, effectively delayed the onset of autoimmune diabetes in human gene replacement non-obese diabetic mice. By spatial proteomics analysis, VLX-1005 treatment resulted in marked reductions in infiltrating T and B cells and macrophages with accompanying increases in immune checkpoint molecule PD-L1, suggesting a shift towards an immune-suppressive microenvironment. RNA sequencing analysis of isolated islets and polarized proinflammatory macrophages revealed significant alteration of cytokine-responsive pathways and a reduction in interferon response after VLX-1005 treatment. Our studies demonstrated that theALOX12human replacement gene mouse provides a platform for the preclinical evaluation of LOX inhibitors and supports VLX-1005 as an inhibitor of human 12-LOX that engages the enzymatic target and alters the inflammatory phenotypes of islets and macrophages to promote the delay of autoimmune diabetes.
Overcrowding Drives Tumor Invasion by Inducing Nanotopographical Transition of Plasma Membrane
Authors: Zhao Xinbin , Tan Min , Li Long , Lin Xubo , Li Zekun , Wang Xiaohuan , Song Bingqi , Guo Zheng , Chen Tailin , Hou Sen , Fan Jiehou , Wang Shijiang , Zhang Yun , Fan Yubo , Du Jing 
Published: July 2024

ABSTRACTDuring the development from epithelial neoplasms to invasive carcinoma, uncontrolled growth and proliferation in a confined space cause tumor cells survive in a prolonged overcrowding condition. However, the role of this aberrant physical stimulus induced by overcrowding in the invasiveness acquisition of epithelial cells remains unclear. Here, we first identified overcrowded cancer cells were more abundant at invasive foci in human cancer samples and mouse xenograft models. Combining with mechanical modelling, genetic manipulations and biophysical measurements, we revealed that prolonged overcrowding induces retentive invasiveness in cancer cells by triggering nanocorrugated topographic transition of plasma membrane. Further study demonstrated that the nanocorrugated topographic transition is induced by overcrowding-increased Laplace pressure and disrupts lipid raft-like domains organization to promote tumor invasion. Finally, suppressing nanocorrugated topographical transition of plasma membrane by strengthening membrane-cortex-attachment resists to tumor cell invasion in a mouse model of oncogenesis. This work reveals the profound effect of tissue-scale mechanical revolution-induced biophysical transition of cancer cells in driving tumor invasion.
Using DeepLabCut-Live to probe state dependent neural circuits of behavior with closed-loop optogenetic stimulation
Authors: Gonzalez Melissa , Gradwell Mark A. , Thackray Joshua K , Patel Komal R. , Temkar Kanaksha K. , Abraira Victoria E. 
Published: July 2024

AbstractBackgroundClosed-loop behavior paradigms enable us to dissect the state-dependent neural circuits underlying behavior in real-time. However, studying context-dependent locomotor perturbations has been challenging due to limitations in molecular tools and techniques for real-time manipulation of spinal cord circuits.New MethodWe developed a novel closed-loop optogenetic stimulation paradigm that utilizes DeepLabCut-Live pose estimation to manipulate primary sensory afferent activity at specific phases of the locomotor cycle in mice. A compact DeepLabCut model was trained to track hindlimb kinematics in real-time and integrated into the Bonsai visual programming framework. This allowed an LED to be triggered to photo-stimulate sensory neurons expressing channelrhodopsin at user-defined pose-based criteria, such as during the stance or swing phase.ResultsOptogenetic activation of nociceptive TRPV1+sensory neurons during treadmill locomotion reliably evoked paw withdrawal responses. Photoactivation during stance generated a brief withdrawal, while stimulation during swing elicited a prolonged response likely engaging stumbling corrective reflexes.Comparison with Existing Methods: This new method allows for high spatiotemporal precision in manipulating spinal circuits based on the phase of the locomotor cycle. Unlike previous approaches, this closed-loop system can control for the state-dependent nature of sensorimotor responses during locomotion.ConclusionsIntegrating DeepLabCut-Live with optogenetics provides a powerful new approach to dissect the context-dependent role of sensory feedback and spinal interneurons in modulating locomotion. This technique opens new avenues for uncovering the neural substrates of state-dependent behaviors and has broad applicability for studies of real-time closed-loop manipulation based on pose estimation.ManuscriptHighlightsClosed-loop system probes state-dependent behaviors at pose-modulated instancesBonsai integrates DeepLabCut models for real-time pose estimation during locomotionPhase-dependent TRPV1+sensory afferent photostimulation elicits context-specific withdrawal responses
Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping
Authors: Zhang Di , Rubio Rodríguez-Kirby Leslie A , Lin Yingxin , Song Mengyi , Wang Li , Wang Lijun , Kanatani Shigeaki , Jimenez-Beristain Tony , Dang Yonglong , Zhong Mei , Kukanja Petra , Wang Shaohui , Chen Xinyi Lisa , Gao Fu , Wang Dejiang , Xu Hang , Lou Xing , Liu Yang , Chen Jinmiao , Sestan Nenad , Uhlén Per , Kriegstein Arnold , Zhao Hongyu , Castelo-Branco Gonçalo , Fan Rong 
Published: July 2024

AbstractThe ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC–RNA–Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag– RNA–Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for the layer-defining transcription factors. In corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions. Together, it suggests a role for layer specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, are transiently activated not only at the core of the LPC lesion, but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, resulting in a valuable data resource to investigate brain development, function and disease.
Parallel evolution of methyltransferases leads to vobasine biosynthesis inTabernaemontana elegansandCatharanthus roseus
Authors: Farzana Maisha , Richardson Matthew Bailey , Deschênes Daniel André Ramey , Mai Zhan , Njoku Destiny Ichechi , Deslongchamps Ghislain , Qu Yang 
Published: July 2024

AbstractMonoterpenoid indole alkaloids (MIA) are one of the largest and most complex alkaloid class in nature, boasting many clinically significant drugs such as anticancer vinblastine and antiarrhythmic ajmaline. Many MIAs undergo nitrogenN-methylation, altering their reactivity and affinity to the biological targets through a straightforward reaction. Remarkably, all known MIAN-methyltransferases (NMT) originate from the neofunctionalization of ancestral γ-tocopherolC-methyltransferases (γTMTs), a phenomenon seemingly unique to the Apocynaceae family. In this study, we unveil and characterize a new γTMT-like enzyme from the plantTabernaemontana elegans(toad tree): perivineNβ-methyltransferase (TePeNMT). TePeNMT and other homologs form a distinct clade in our phylogenetic study, setting them apart from other γTMTs and γTMT-like NMTs discovered to date. Enzyme kinetic experiments and enzyme homology modeling studies reveal the significant differences in enzyme active sites between TePeNMT and CrPeNMT, a previously characterized perivineNβ-methyltransferase fromCatharanthus roseus(Madagascar periwinkle). Collectively, our findings suggest that parallel evolution of ancestral γTMTs may be responsible for the occurrence of perivineN-methylation inT. elegansandC. roseus.
Synergy and antagonism in the integration of BCR and CD40 signals that control B-cell proliferation
Authors: Huang Helen , Vaidehi Narayanan Haripriya , Hoffmann Alexander 
Published: July 2024

ABSTRACTIn response to infection or vaccination, a successful antibody response must enrich high-affinity antigen-reactive B-cells through positive selection, but eliminate auto-reactive B-cells through negative selection. B-cells receive signals from the B-cell receptor (BCR) which binds the antigen, and the CD40 receptor which is stimulated by neighboring T-cells that also recognize the antigen. How BCR and CD40 signaling are integrated quantitatively to jointly determine B-cell fate decision and proliferation remains unclear. To investigate this, we developed a differential-equations-based model of the BCR and CD40 signaling networks activating NFκB. Our model accurately recapitulates the NFκB dynamics of B-cells stimulated through their BCR and CD40 receptors, correctly predicting that costimulation induces more NFκB activity. However, when linking it to established cell fate decision models of cell survival and cell cycle control, it predicted potentiated population expansion that was not observed experimentally. We found that this discrepancy was due to a time-dependent functional antagonism exacerbated by BCR-induced caspase activity that can trigger apoptosis in founder cells, unless NFκB-induced survival gene expression protects B-cells in time. Guided by model predictions, sequential co-stimulation experiments revealed how the temporal dynamics of BCR and CD40 signaling control the fate decision between negative and positive selection of B-cell clonal expansion. Our quantitative findings highlight a complex non-monotonic integration of BCR and CD40 signals that is controlled by a balance between NFκB and cell-death pathways, and suggest a mechanism for regulating the stringency of B-cell selection during an antibody response.HighlightsCD40 and BCR signaling in B-cells synergize to potentiate NFκB cRel activationBCR-apoptotic signaling may enhance or antagonize CD40-driven proliferationBCR-induced apoptosis may be rescued by CD40 within a temporal windowA mathematical model reveals regulators of the dose-dependent selection stringency
The Role of TandemHeartTMcombined with ProtekDuoTMas Right Ventricular Support Device: A Simulation Approach
Authors: De Lazzari Beatrice , Badagliacca Roberto , Capoccia Massimo , Maybauer Marc O , De Lazzari Claudio 
Published: July 2024

AbstractRight ventricular failure increases short-term mortality in the setting of acute myocardial infarction, cardiogenic shock, advanced left-sided heart failure and pulmonary hypertension. Right ventricular failure remains quite a challenging condition to manage in view of its complex background and still incomplete understanding of its pathophysiology. Percutaneous and surgically implanted right ventricular assist devices (RVADs) have been investigated in different clinical settings. The use of the ProtekDuoTM(LivaNova, London, UK) is currently a promising approach due to its features such as groin-free approach leading to early mobilisation, easy percutaneous deployment, compatibility with different pumps and oxygenators, and adaptability to different configurations. The aim of this work was to simulate the behaviour of the TandemHeartTMpump applied “in series” and “in parallel“ mode and the combination of TandemHeartTMand ProtekDuoTMcannula as right ventricular assist device using CARDIOSIM©software simulator platform. The effects induced on the main hemodynamic and energetic variables were analysed for both the right atrial-pulmonary arterial and right ventricular-pulmonary arterial configuration with different pump rotational speed and following of Milrinone administration. The TandemHeartTMincreased right ventricular end systolic volume by 10%, larger increases were evident for higher speeds (6000 and 7500 rpm) and connections with 21 Fr inflow and 17 Fr outflow cannula, respectively. Both TandemHeartTMand ProtekDuoTMsupport increased left ventricular preload. When different RVAD settings were used, Milrinone therapy increased the left ventricular pressure-volume area and decreased the right pressure-volume area slightly. A reduction in oxygen consumption (demand) was observed with reduced right stroke work and pressure volume area and increased oxygen supply (coronary blood flow).