bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose metabolism controls monocyte homeostasis and migration but has no impact on atherosclerosis development in mice
Authors: Gallerand Alexandre , Dolfi Bastien , Stunault Marion I. , Caillot Zakariya , Castiglione Alexia , Strazzulla Axelle , Chen Chuqiao , Heo Gyu Seong , Luehmann Hannah , Batoul Flora , Vaillant Nathalie , Dumont Adélie , Pilot Thomas , Merlin Johanna , Zair Fairouz N. , Gilleron Jerome , Bertola Adeline , Carmeliet Peter , Williams Jesse W. , Arguello Rafael J. , Masson David , Dombrowicz David , Yvan-Charvet Laurent , Doyen Denis , Haschemi Arvand , Liu Yongjian , Guinamard Rodolphe R. , Ivanov Stoyan 
Published: October 2024

AbstractMonocytes directly contribute to atherosclerosis development by their recruitment to plaques in which they differentiate into macrophages. In the present study, we ask how modulating monocyte glucose metabolism could affect their homeostasis and their impact on atherosclerosis. Here we investigate how circulating metabolites control monocyte behavior in blood, bone marrow and peripheral tissues of mice. We find that serum glucose concentrations correlate with monocyte numbers. In diet-restricted mice, monocytes fail to metabolically reprogram from glycolysis to fatty acid oxidation, leading to reduced monocyte numbers in the blood. Mechanistically, Glut1-dependent glucose metabolism helps maintain CD115 membrane expression on monocytes and their progenitors, and regulates monocyte migratory capacity by modulating CCR2 expression. Results from genetic models and pharmacological inhibitors further depict the relative contribution of different metabolic pathways to the regulation of CD115 and CCR2 expression. Meanwhile, Glut1 inhibition does not impact atherosclerotic plaque development in mouse models despite dramatically reducing blood monocyte numbers, potentially due to the remaining monocytes having increased migratory capacity. Together, these data emphasize the role of glucose uptake and intracellular glucose metabolism in controlling monocyte homeostasis and functions.
Transient nicotine exposure in early adolescent male mice freezes their dopamine circuits in an immature state
Authors: Reynolds Lauren M. , Gulmez Aylin , Fayad Sophie L. , Campos Renan Costa , Rigoni Daiana , Nguyen Claire , Le Borgne Tinaïg , Topilko Thomas , Rajot Domitille , Franco Clara , Fernandez Sebastian P. , Marti Fabio , Heck Nicolas , Mourot Alexandre , Renier Nicolas , Barik Jacques , Faure Philippe 
Published: October 2024

AbstractHow nicotine acts on developing neurocircuitry in adolescence to promote later addiction vulnerability remains largely unknown, but may hold the key for informing more effective intervention efforts. We found transient nicotine exposure in early adolescent (PND 21-28) male mice was sufficient to produce a marked vulnerability to nicotine in adulthood (PND 60 + ), associated with disrupted functional connectivity in dopaminergic circuits. These mice showed persistent adolescent-like behavioral and physiological responses to nicotine, suggesting that nicotine exposure in adolescence prolongs an immature, imbalanced state in the function of these circuits. Chemogenetically resetting the balance between the underlying dopamine circuits unmasked the mature behavioral response to acute nicotine in adolescent-exposed mice. Together, our results suggest that the perseverance of a developmental imbalance between dopamine pathways may alter vulnerability profiles for later dopamine-dependent psychopathologies.
Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma
Authors: Karlsson Jenny , Yasui Hiroaki , Mañas Adriana , Andersson Natalie , Hansson Karin , Aaltonen Kristina , Jansson Caroline , Durand Geoffroy , Ravi Naveen , Ferro Michele , Yang Minjun , Chattopadhyay Subhayan , Paulsson Kajsa , Spierings Diana , Foijer Floris , Valind Anders , Bexell Daniel , Gisselsson David 
Published: October 2024

AbstractNeuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicate these two contrasting scenarios and show branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.
Molecular mechanisms of re-emerging chloramphenicol susceptibility in extended-spectrum beta-lactamase-producing Enterobacterales
Authors: Graf Fabrice E. , Goodman Richard N. , Gallichan Sarah , Forrest Sally , Picton-Barlow Esther , Fraser Alice J. , Phan Minh-Duy , Mphasa Madalitso , Hubbard Alasdair T. M. , Musicha Patrick , Schembri Mark A. , Roberts Adam P. , Edwards Thomas , Lewis Joseph M. , Feasey Nicholas A. 
Published: October 2024

AbstractInfections with Enterobacterales (E) are increasingly difficult to treat due to antimicrobial resistance. After ceftriaxone replaced chloramphenicol (CHL) as empiric therapy for suspected sepsis in Malawi in 2004, extended-spectrum beta-lactamase (ESBL)-E rapidly emerged. Concurrently, resistance to CHL in Escherichia coli and Klebsiella spp. decreased, raising the possibility of CHL re-introduction. However, many phenotypically susceptible isolates still carry CHL acetyltransferase (cat) genes. To understand the molecular mechanisms and stability of this re-emerging CHL susceptibility we use a combination of genomics, phenotypic susceptibility assays, experimental evolution, and functional assays for CAT activity. Here, we show that of 840 Malawian E. coli and Klebsiella spp. isolates, 31% have discordant CHL susceptibility genotype–phenotype, and we select a subset of 42 isolates for in-depth analysis. Stable degradation of cat genes by insertion sequences leads to re-emergence of CHL susceptibility. Our study suggests that CHL could be reintroduced as a reserve agent for critically ill patients with ESBL-E infections in Malawi and similar settings and highlights the ongoing challenges in inferring antimicrobial resistance from sequence data.
Population variability in X-chromosome inactivation across 10 mammalian species
Authors: Werner Jonathan M. , Hover John , Gillis Jesse 
Published: October 2024

AbstractOne of the two X-chromosomes in female mammals is epigenetically silenced in embryonic stem cells by X-chromosome inactivation. This creates a mosaic of cells expressing either the maternal or the paternal X allele. The X-chromosome inactivation ratio, the proportion of inactivated parental alleles, varies widely among individuals, representing the largest instance of epigenetic variability within mammalian populations. While various contributing factors to X-chromosome inactivation variability are recognized, namely stochastic and/or genetic effects, their relative contributions are poorly understood. This is due in part to limited cross-species analysis, making it difficult to distinguish between generalizable or species-specific mechanisms for X-chromosome inactivation ratio variability. To address this gap, we measure X-chromosome inactivation ratios in ten mammalian species (9531 individual samples), ranging from rodents to primates, and compare the strength of stochastic models or genetic factors for explaining X-chromosome inactivation variability. Our results demonstrate the embryonic stochasticity of X-chromosome inactivation is a general explanatory model for population X-chromosome inactivation variability in mammals, while genetic factors play a minor role.
Climate justice beliefs related to climate action and policy support around the world
Authors: Ogunbode Charles A. , Doran Rouven , Ayanian Arin H. , Park Joonha , Utsugi Akira , van den Broek Karlijn L. , Ghorayeb Jihane , Aquino Sibele D. , Lins Samuel , Aruta John J. B. R. , Reyes Marc E. S. , Zick Andreas , Clayton Susan 
Published: October 2024

AbstractClimate justice is increasingly prominent in climate change communication and advocacy but little is known about public understanding of the concept or how widely it resonates with different groups. In our global survey of 5,627 adults in 11 countries spanning the global north and south, most participants (66.2%) had never heard of climate justice. Nonetheless, endorsement of climate justice beliefs was widespread (for example, acknowledging the disproportionate impact of climate change on poor people and the underpinning roles of capitalism and colonialism in the climate crisis). Climate justice beliefs were also associated with various indices of climate action and policy support. These associations tended to be stronger in countries with high GHG emissions and where social inequality is also more politically salient. The results highlight the value of climate justice as a motive for climate action across diverse geographical contexts.
Executive function in children with neurodevelopmental conditions: a systematic review and meta-analysis
Authors: Sadozai Ayesha K. , Sun Carter , Demetriou Eleni A. , Lampit Amit , Munro Martha , Perry Nina , Boulton Kelsie A. , Guastella Adam J. 
Published: October 2024

AbstractExecutive function (EF) delays are well documented in paediatric neurodevelopmental conditions (NDCs). There is no consensus about whether EF delay represents a transdiagnostic feature of NDCs. This systematic review and meta-analysis synthesized 180 studies reporting two or more NDC comparisons on EF, examined differences between NDCs, and the moderating effects of gender, age, publication year, DSM editions and assessment types. Studies using established EF measures across seven domains (attention, fluency, set-shifting, set-switching, response inhibition, planning and working memory) in participants under 18 were included. Summary effects were compared: (1) for all reported NDCs relative to control, (2) for each individual NDC relative to control and (3) between NDC groups. Results confirmed that EF delay was a transdiagnostic feature of neurodevelopmental delay, with a moderate effect size of delay across all NDCs (g = 0.56, 95% confidence interval (CI) 0.49–0.63) compared with control. This effect increased with comorbidities (g = 0.72, 95% CI 0.59–0.86), DSM-5 criteria and informant measures. Comparisons between NDCs revealed few differences: children with tic disorders (TD) showed smaller EF delays, children with attention-deficit/hyperactivity disorder (ADHD) showed larger delays in attention, response inhibition, planning and working memory compared with TD and specific learning disorders, while children with autism spectrum disorders showed greater delays on set-switching compared with ADHD. Findings support transdiagnostic models of neurodevelopment to further a developmentally sensitive science that can reveal how EF delays contribute to brain circuitry, symptom profiles and functioning, and ultimately support early interventions and outcomes for all children with NDCs.
Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues
Authors: Chang Lei , Xie Yang , Taylor Brett , Wang Zhaoning , Sun Jiachen , Armand Ethan J. , Mishra Shreya , Xu Jie , Tastemel Melodi , Lie Audrey , Gibbs Zane A. , Indralingam Hannah S. , Tan Tuyet M. , Bejar Rafael , Chen Clark C. , Furnari Frank B. , Hu Ming , Ren Bing 
Published: October 2024

AbstractCurrent methods for analyzing chromatin architecture are not readily scalable to heterogeneous tissues. Here we introduce Droplet Hi-C, which uses a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture of the mouse cortex and analyzed gene regulatory programs in major cortical cell types. In addition, we used this technique to detect copy number variations, structural variations and extrachromosomal DNA in human glioblastoma, colorectal and blood cancer cells, revealing clonal dynamics and other oncogenic events during treatment. We refined the technique to allow joint profiling of chromatin architecture and transcriptome in single cells, facilitating exploration of the links between chromatin architecture and gene expression in both normal tissues and tumors. Thus, Droplet Hi-C both addresses critical gaps in chromatin analysis of heterogeneous tissues and enhances understanding of gene regulation.
Mechanism of polyadenylation-independent RNA polymerase II termination
Authors: Rengachari Srinivasan , Hainthaler Thomas , Oberthuer Christiane , Lidschreiber Michael , Cramer Patrick 
Published: October 2024

Abstract
The mechanisms underlying the initiation and elongation of RNA polymerase II (Pol II) transcription are well-studied, whereas termination remains poorly understood. Here we analyze the mechanism of polyadenylation-independent Pol II termination mediated by the yeast Sen1 helicase. Cryo-electron microscopy structures of two pretermination intermediates show that Sen1 binds to Pol II and uses its adenosine triphosphatase activity to pull on exiting RNA in the 5′ direction. This is predicted to push Pol II forward, induce an unstable hypertranslocated state and destabilize the transcription bubble, thereby facilitating termination. This mechanism of transcription termination may be widely used because it is conceptually conserved in the bacterial transcription system.
Rational design and synthesis of new pyrrolone candidates as prospective insecticidal agents against Culex pipiens L. Larvae
Authors: Hekal Mohamed H. , Hashem Ahmed I. , El-Azm Fatma S.M. Abu , Abdel-Haleem Doaa R. , Rafat El-Hady , Ali Yasmeen M. 
Published: October 2024

AbstractAs a result of its high reactivity, furan-2(3H)-one derivative 2 can be selected as a versatile and suitable candidate for building of novel nitrogen heterocyclic compounds. Consequently, furan-2(3H)-one derivative 2 and some nitrogen nucleophiles were utilized as starting materials for the formation of new pyridazinone and pyrrolone derivatives bearing naphthalene moiety. The continuous buildup of insecticide resistance is the main obstacle facing pest control measures. Pyrrole-based insecticides are a favourable choice due to their unique mode of action and no cross-resistance with traditional neurotoxic insecticides. The larvicidal activities of pyrrolone derivatives were assessed against field and laboratory strains of Culex pipiens larvae in comparison with chlorfenapyr (pyrrole insecticide). Compounds 17 (21.05 µg/mL) > 9 (22.81 µg/mL) > 15 (24.39 µg/mL) > 10 (26.76 µg/mL) > 16 (32.09 µg/mL) were most effective against lab strain of C. pipiens larvae relative to chlorfenapyr (25.43 µg/mL). While in field strain, 17 and 15 were the most toxic compounds followed by 9 > 10 > 16 > 2 with LC50 of 9.87, 10.76, 11.52, 12.68, 15.32 and 18.37 µg/mL, respectively, compared with chlorfenapyr with 14.03 µg/mL. The cytochrome P-450 monooxygenase activities were significantly increased in treated larvae of lab and field strains relative to untreated. The great variations in toxicity of the synthesized compounds were interpreted by structure-activity relationship study. The pyrrolone derivatives are effective against field and insecticide-resistant strains. Therefore, they are considered promising compounds to be integrated into pest management programs.
Loss of Stim2 in zebrafish induces glaucoma-like phenotype
Authors: Baranykova Sofiia , Gupta Rishikesh Kumar , Kajdasz Arkadiusz , Wasilewska Iga , Macias Matylda , Szybinska Aleksandra , Węgierski Tomasz , Nahia Karim Abu , Mondal Shamba S. , Winata Cecilia L. , Kuźnicki Jacek , Majewski Lukasz 
Published: October 2024

AbstractCalcium is involved in vision processes in the retina and implicated in various pathologies, including glaucoma. Rod cells rely on store-operated calcium entry (SOCE) to safeguard against the prolonged lowering of intracellular calcium ion concentrations. Zebrafish that lacked the endoplasmic reticulum Ca2+ sensor Stim2 (stim2 knockout [KO]) exhibited impaired vision and lower light perception-related gene expression. We sought to understand mechanisms that are responsible for vision impairment in stim2 KO zebrafish. The single-cell RNA (scRNA) sequencing of neuronal cells from brains of 5 days postfertilization larvae distinguished 27 cell clusters, 10 of which exhibited distinct gene expression patterns, including amacrine and γ-aminobutyric acid (GABA)ergic retinal interneurons and GABAergic optic tectum cells. Five clusters exhibited significant changes in cell proportions between stim2 KO and controls, including GABAergic diencephalon and optic tectum cells. Transmission electron microscopy of stim2 KO zebrafish revealed decreases in width of the inner plexiform layer, ganglion cells, and their dendrites numbers (a hallmark of glaucoma). GABAergic neuron densities in the inner nuclear layer, including amacrine cells, as well as photoreceptors significantly decreased in stim2 KO zebrafish. Our study suggests a novel role for Stim2 in the regulation of neuronal insulin expression and GABAergic-dependent vision causing glaucoma-like retinal pathology.
Glyceroniosomes for enhanced intestinal absorption of hydrochlorothiazide and lisinopril in their fixed dose combination
Authors: Elbasuony Aya R. , Abdelaziz Abdelaziz E. , Mazyed Eman A. , El Maghraby Gamal M. 
Published: October 2024

AbstractThe objective was to investigate the effect of co-administration of hydrochlorothiazide and lisinopril as fixed dose combination on their intestinal absorption. The scope was extended to enhance intestinal absorption of both drugs. In situ rabbit intestinal absorption through the duodenum and jejuno-ileum was used to monitor membrane permeability of both drugs when perfused alone or in combination. Niosomes containing glycerols (glyceroniosomes) were loaded with both drugs. Glyceroniosomes comprised Span 60 or Tween 40 in combination with cholesterol and glycerol were prepared by bath sonication. Glyceroniosomes were characterized with respect to vesicle size, drug entrapment efficiency and were examined using transmission electron microscope (TEM). The prepared vesicles were nanosized spherical vesicles with average size of 202.4 nm and 108.8 nm for span free and span containing glyceroniosomes, respectively. The recorded Zeta potential values suggested good stability of the prepared formulations. Intestinal absorption studies reflected incomplete absorption of hydrocholothiazide and lisinopril correlating with their categorization as class IV and III drugs, respectively. Co-perfusion of both drugs reduced the intestinal absorption of lisinopril. Simultaneous encapsulation in glyceroniosomes enhanced the intestinal absorption of both drugs. Tween based systems were more efficient. The study introduced glyceroniosomes as carriers of simultaneous delivery of hydrochlorothiazide and lisinopril.
Computed tomography for the detection of myocardial hypoperfusion in acute myocardial infarction and the associated CT-to-catheter time
Authors: Mostafa Karim , Seoudy Hatim , Aludin Schekeb , Schunk Domagoj , Peckolt Hannes , Wolf Carmen , Saad Mohammed , Both Marcus , Jansen Olav , Frank Derk , Langguth Patrick 
Published: October 2024

AbstractEmergency computed tomography (CT) often does not allow for comprehensive coronary artery assessment. However, CT may reveal pathological myocardial hypoperfusion suggestive of acute myocardial infarction (AMI), especially in patients presenting with a different diagnostic hypothesis. CT hypoperfusion is known to be associated with myocardial infarction, however the diagnostic value of CT hypoperfusion for the detection of AMI is still not well evaluated. This was a single-centre retrospective study including patients who underwent invasive coronary angiography (ICA) due to suspected AMI based on incidental perfusion defects upon emergency CT imaging between 2018 and 2023. A total of 22 patients (mean age 66.3 ± 10.8 years, 11 female) were included in this analysis. The diagnosis of AMI was established in all cases leading to ICA. Culprit coronary artery lesions with an indication of percutaneous coronary intervention were detected in all patients who underwent ICA. Spearmann correlation for hypoperfused segments on CT imaging and the corresponding vascular territory upon ICA was significantly substantial (ρ = 0.73, p = < 0.001). The higher the number of affected myocardial segments, the faster ICA was initiated. Mean time between the suspicion of AMI on CT imaging and ICA was 196 (29–4044) minutes. Myocardial hypoperfusion on emergency CT imaging should be considered as AMI until proven otherwise, independent of the clinical scenario leading to performance of CT imaging and whether imaging was performed for the exclusion of non-cardiac pathologies. Early initiation of further diagnostic workup may potentially avoid delays to invasive treatment and reduce the CT-to-catheter-time. Our study explicitly underlines that myocardial hypoperfusion upon contrast enhanced CT imaging needs to be considered as sign of acute myocardial infarction and indicates targeted clinical workup to rule out this diagnosis and to shorten the timeframe from imaging diagnosis to interventional treatment.
The mitochondrial long non-coding RNA lncMtloop regulates mitochondrial transcription and suppresses Alzheimer’s disease
Authors: Xiong Wandi , Xu Kaiyu , Sun Jacquelyne Ka-Li , Liu Siling , Zhao Baizhen , Shi Jie , Herrup Karl , Chow Hei-Man , Lu Lin , Li Jiali 
Published: October 2024

AbstractMaintaining mitochondrial homeostasis is crucial for cell survival and organismal health, as evidenced by the links between mitochondrial dysfunction and various diseases, including Alzheimer’s disease (AD). Here, we report that lncMtDloop, a non-coding RNA of unknown function encoded within the D-loop region of the mitochondrial genome, maintains mitochondrial RNA levels and function with age. lncMtDloop expression is decreased in the brains of both human AD patients and 3xTg AD mouse models. Furthermore, lncMtDloop binds to mitochondrial transcription factor A (TFAM), facilitates TFAM recruitment to mtDNA promoters, and increases mitochondrial transcription. To allow lncMtDloop transport into mitochondria via the PNPASE-dependent trafficking pathway, we fused the 3’UTR localization sequence of mitochondrial ribosomal protein S12 (MRPS12) to its terminal end, generating a specified stem-loop structure. Introducing this allotropic lncMtDloop into AD model mice significantly improved mitochondrial function and morphology, and ameliorated AD-like pathology and behavioral deficits of AD model mice. Taken together, these data provide insights into lncMtDloop as a regulator of mitochondrial transcription and its contribution to Alzheimer’s pathogenesis
Electrophoretic assisted fabrication of additive-free WS2 nanosheet anodes for high energy density lithium-ion batteries
Authors: Pham Xuan-Manh , Patil Niraj Nitish , Abdul Ahad Syed , Kapuria Nilotpal , Owusu Kwadwo Asare , Geaney Hugh , Singh Shalini , Ryan Kevin M. 
Published: October 2024

2D WS2 were synthesized via the hot-injection method, followed by their electrophoretic deposition (EPD) on the current collector. EPD is an effective approach to fabricating additive-free anodes, thereby greatly boosting the energy density of LIBs.