bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Kidney Organoid Microphysiological Analysis Platform
Authors: Hong SoonGweon , Song Minsun , Miyoshi Tomoya , Morizane Ryuji , Bonventre Joseph V. , Lee Luke P. 
Published: October 2024

ABSTRACTKidney organoids, replicating human development, pathology, and drug responses, are a promising model for advancing bioscience and pharmaceutical innovation. However, reproducibility, accuracy, and quantification challenges hinder their broader utility for advanced biological and pharmaceutical applications. Herein, we present a dynamic kidney organoid microphysiological analysis platform (MAP), designed to enhance organoid modeling and assays within physiologically relevant environments, thereby expanding their utility in advancing kidney physiology and pathology research. First, precise control of the dynamic microenvironment in MAP enhances the ability to fine-tune nephrogenic intricacies, facilitating high-throughput and reproducible human kidney organoid development. Also, MAP’s miniaturization of kidney organoids significantly advances pharmaceutical research by allowing for detailed analysis of entire nephron segments, which is crucial for assessing the nephrotoxicity and safety of drugs. Furthermore, the MAP’s application in disease modeling faithfully recapitulates pathological development and functions as a valuable testbed for therapeutic exploration in polycystic kidney diseases. We envision the kidney organoid MAP enhancing pharmaceutical research, standardizing processes, and improving analytics, thereby elevating the quality and utility of organoids in biology, pharmacology, precision medicine, and education.
New proteomic signature in circulating extracellular vesicles from tumor-draining vein of lung adenocarcinomas patients
Authors: Tricard Jérémy , Durand Stéphanie , Gateau Amy , Negroni Luc , Chaunavel Alain , Bertin François , Conti Massimo , Akil Hussein , Lalloué Fabrice 
Published: October 2024

ABSTRACTIdentification of noninvasive prognostic biomarkers, allowing monitoring of frequently developed relapse in patients with locally advanced non-small cell lung cancer (NSCLC), still of primary importance. Tumor-draining vein (TDV) plasma samples, are known to be enriched in circulating cancer biomarkers compared to samples from peripheral vein (PV). Thus, we thought to investigate the proteomic profile of extracellular vesicles (EVs) from TDV compared to those from PV plasma samples of patients operated for NSCLC.Purified EVs from TDV and PV plasma samples were characterized for their size distribution and concentration using nanoparticles tracking analysis (NTA). Proteomic profiling of TDV-derived EVs and PV-derived EVs were further done using mass spectrometry (nanoLC-MS/MS) analysis. In parallel, proteomic profile of tumoral and non-tumoral adjacent counterpart tissues from patients with NSCLC were investigated.Twenty patients with NSCLC, treated by surgery with curative intent, were enrolled in this study. We showed that EVs from TDV plasma samples were significantly smaller than those from PV plasma samples. Interestingly, the concentration of TDV-derived EVs were significantly higher than PV-derived EVs. However, EVs concentration and size were not associated with tumor size or other clinical characteristics. Proteomic profiling showed that 9 of the 10 most overexpressed proteins in EVs from TDV samples compared to those from PV, were associated with lung cancer diagnosis and prognosis. Remarkably, 1 protein (SRPRB) was commonly upregulated in lung tumor tissues (as compared to non-tumoral counterparts) and in TDV-derived EVs (as compared to PV-derived EVs). In contrast, 12 proteins were found to be upregulated in TDV-derived EVs and downregulated in tumor tissues.In conclusion, all of these identified proteins, carried by EVs from TDV plasma samples, might represent promising novel biomarkers for NSCLC prognosis and predicting recurrences at early stages.
Assessing Technical College Students’ Biology Proficiency as Related to Gender and Performance in Biology in Nigeria
Authors: Sowunmi Kehinde , Enoch Ajoa Iyanu , Uchenna Ogbonnaya 
Published: October 2024

AbstractThis study investigated biology proficiency in relation to gender and performance among 350 Nigerian technical college students from 5 elitist technical colleges in Lagos State, employing a quantitative research method within a descriptive survey design. Data collected were analysed using descriptive statistics of frequency, percentage, mean, and standard deviation, alongside inferential statistics including independent samples t-test and multiple regression analysis. Findings revealed that technical college students from elitist schools displayed a high level of biology proficiency. Significant correlations were found among students conceptual understanding, procedural knowledge, strategic competence, adaptive reasoning, productive disposition, and overall performance in biology. While gender differences in biology proficiency appear to be diminishing across most subscales, subtle gender differences were observed in performance in biology in this study. Gender, conceptual understanding, productive disposition, adaptive reasoning, strategic competence, and procedural knowledge made statistically significant contributions to the variance in technical college students performance in biology. Based on this baseline study, it is recommended that future research in Nigeria should explore the biology proficiency of non-elitist schools, which constitute the majority of educational institutions in the country, to enable broader generalization of these findings.
Temperate phages increase antibiotic effectiveness in aCaenorhabditis elegansinfection model
Authors: Fatima Rabia , MacNeil Lesley T. , Hynes Alexander P. 
Published: October 2024

AbstractThe bactericidal nature of obligately lytic bacterial viruses (phages) is of increasing interest for the treatment of drug-resistant bacterial infections, either administered alone or in combination with antibiotics. In contrast, temperate phages are largely ignored in a therapeutic context due to their ability to lie dormant within the bacterial host. However, these phages often undergo a lytic cycle. Furthermore, even in their dormant state their carriage can be a considerable burden to the bacterium – most famously by their ability to switch to lytic replication in response to environmental triggers, such as antibiotics, that stress the bacterial host. Recent reports of antibiotics synergizing uniquely with temperate phagesin vitro, termed “temperate phage antibiotic synergy” (tPAS), present a potentially scalable opportunity to make use of these abundant entities for the treatment of bacterial infections. Here we employCaenorhabditis elegansas a robustin vivoanimal model for testing the efficacy of temperate phages as adjuvants to antibiotics.In vivo, the antibiotic ciprofloxacin can abolish dormancy of temperate phage Hali - infecting a ciprofloxacin resistantPseudomonas aeruginosaclinical strain - while in the absence of the antibiotic dormancy events explain 60% of the bacterial survivors. The Phage Hali-ciprofloxacin pairing increased the lifespan ofP. aeruginosainfected worms to that of the uninfected control, at doses where neither the phage nor the antibiotic had any effect alone. Complete rescue was also observed in worms infected with a phage-carrying strain treated with the otherwise ineffective antibiotic, supporting that the phage - even in its dormant form - can greatly enhance antibiotic effectiveness. This illustrates potential “accidental” phage therapy when antibiotics are normally prescribed. Our work establishesC. elegansas a suitable model for studying thein vivoefficacy of tPAS and is the firstin vivodemonstration of this synergy, greatly expanding the therapeutic potential of temperate phages.
Age, sex, and mitochondrial-haplotype influence gut microbiome composition and metabolites in a genetically diverse rat model
Authors: Nguyen Hoang Van M. , Cabello Eleana , Dyer David , Fender Chloe , Garcia-Jaramillo Manuel , Hord Norman G. , Austad Steven , Richardson Arlan , Unnikrishnan Archana 
Published: October 2024

AbstractWe evaluated the impact of sex and mitochondrial-haplotype on the age-related changes in the fecal gut microbiome of the genetically heterogeneous rodent model, the OKC-HETB/Wrat. Alpha-diversity, measuring richness and evenness of gut microbiome composition, did not change with age or mitochondrial-haplotype. However, beta-diversity, a measure of microbial differences among samples, was significantly modulated by age in male and female rats in both mitochondrial-haplotypes. The age-related changes in the microbiome differed markedly between male and female rats. Five microbial species changed significantly with age in male rats compared to nine microbial species in female rats. Only three of these microbes changed with age in both male and female rats. The mitochondrial-haplotype of the rats also affected how aging altered the microbiome. Interestingly, most of the microbial species that changed significantly with age were mitochondrial-haplotype and sex specific, i.e., changing in one sex and not the other. We also discovered that sex and mitochondrial-haplotype significantly affected the age-related variations in content of fecal short-chain fatty acids and plasma metabolites that influence or are regulated by the microbiome, e.g., tryptophan derived metabolites and bile acids. This study demonstrates that the host’s sex plays a significant role in how the gut microbiome evolves with age, even within a genetically diverse background. Importantly, this is the first study to show that the mitochondrial-haplotype of a host impacts the age-related changes in the microbiome and supports previous studies suggesting a bidirectional interaction between the gut microbiome and host mitochondria.HighlightsMost age-related changes in microbial species occurred in one sex but not the otherMitochondrial-haplotype altered the microbiome and was generally sex dependentMicrobiome associated metabolites differed by age, sex, and mitochondria-haplotype
Health outcomes after national acute sleep deprivation events among the American public
Authors: Kelly Neil J. , Chaudhary Rahul , El Khoury Wadih , Kalepalli Nishita , Wang Jesse , Patel Priya , Chan Irene N. , Rahman Haris , Saiyed Aisha , Shah Anisha N. , McClung Colleen A. , Okawa Satoshi , Nouraie Seyed Mehdi , Chan Stephen Y. 
Published: October 2024

AbstractBackgroundSleep is increasingly recognized as essential to human health, yet the adverse health consequences of acute sleep deprivation are unknown. Using actigraphic, genomic, and health data from theAll of Us(AoU) Research Program, we characterized the detrimental health consequences of acute sleep deprivation in the American public.MethodsLOESS smoothing was performed on sleep estimates from Fitbit users (N = 14,681) between June 1, 2016 and July 1, 2022. Dates when population minutes slept were less than the 90% confidence interval of the LOESS regression were named acute sleep deprivation events (ASDEs). Phenome-wide disease incidence among theAoUpopulation (N = 287,012) in the 10 days post-ASDE was compared to a preceding reference period by McNemar test. Circadian rhythm and sleep duration-associated SNPs were screened to identify genotypes associated with shorter ASDE sleep duration. Influences of sleep and circadian genotype on post-ASDE influenza risk were modeled using binomial family generalized estimating equations.FindingsWe identified 32 ASDEs spanning political and non-political events. A phenome-wide screen found increased risk of influenza (OR = 1.54 [1.40, 1.70],P-value = 1.00 x 10-18) following ASDEs. 56 SNPs were associated with decreased sleep duration on ASDEs. Higher quantiles of ASDE-related SNP genotype burden were associated with less ASDE sleep duration and a greater risk of influenza-associated healthcare visits.InterpretationNational political and non-political events are associated with acute sleep deprivation and greater influenza risk which is amplified by sleep genotypes. These findings should inform public health vigilance surrounding major national events.
Essential role of Hepcidin in host resistance to disseminated candidiasis
Authors: Arekar Tanmay , Katikaneni Divya , Kasem Sadat , Desai Dhruv , Acharya Thrisha , Cole Augustina , Khodayari Nazli , Vaulont Sophie , Hube Bernhard , Nemeth Elizabeta , Drakesmith Alexander , Lionakis Michail S , Mehrad Borna , Scindia Yogesh 
Published: October 2024

SUMMARYCandida albicansis a leading cause of life-threatening invasive infections with up to 40% mortality rates in hospitalized individuals despite antifungal therapy. Patients with chronic liver disease are at an increased risk of candidemia, but the mechanisms underlying this susceptibility are incompletely defined. One consequence of chronic liver disease is attenuated ability to produce hepcidin and maintain organismal control of iron homeostasis. To address the biology underlying this critical clinical problem, we demonstrate the mechanistic link between hepcidin insufficiency and candida infection using genetic and inducible hepcidin knockout mice. Hepcidin deficiency led to unrestrained fungal growth and increased transition to the invasive hypha morphology with exposed 1,3, β-glucan that exacerbated kidney injury, independent of the fungal pore-forming toxin candidalysin in immunocompetent mice. Of translational relevance, the therapeutic administration of PR-73, a hepcidin mimetic, improved the outcomes of infection. Thus, we identify hepcidin deficiency as a novel host susceptibility factor againstC. albicansand hepcidin mimetics as a potential intervention.
Task-irrelevant features in working memory alter current visual processing
Authors: Shi Hongqiao , Zhang Qiqi , Zhou Jieyudong , Ding Yue , Wang Yonghui , Li Ya 
Published: October 2024

AbstractHigher-level cognition depends on visual working memory (VWM), the ability of our brain to maintain and manipulate internal representations of images that are no longer presented to us. An important question in this field is whether VWM is represented in a sensory or nonsensory manner. Progress has been made in understanding the features to be remembered, but the representational nature of the memory-irrelevant features is unclear. Here, we used a dual-task paradigm to investigate how and when the memory-irrelevant features interact with the concurrent visual information. In a series of experiments, participants were asked to perform a visual search task (Experiment 1) or a perceptual discrimination task (Experiments 2 and 3) involving a memory- irrelevant feature while simultaneously holding the other feature for later retrieval. Experiment 1 showed that VWM biases the allocation of attention to color matching to the memory-irrelevant color. More importantly, the degree of VWM-biased attention decreased monotonically with decreasing feature similarity, and this behavioral monotonic gradient profile resembled the tuning curve of feature-selective neurons in the early visual cortex. Experiment 2 revealed that irrelevant features biased ongoing perception, as indicated by the shifted discrimination threshold. Experiment 3 further demonstrated that VWM-biased perception occurs only at short delays but not at prolonged delays. Our results suggest that the memory-irrelevant feature is represented as a sensory analog for a limited period of time in the visual areas where it was initially processed. Our results extend sensory recruitment theory to memory-irrelevant features in VWM.
Resistance of E2F4DN to p38MAPKphosphorylation attenuates DNA damage-induced neuronal death via Cited2
Authors: Llabrés-Mas Aina María , Garrido-García Alberto , Cano-Daganzo Vanesa , Frade José M. 
Published: October 2024

AbstractE2F4, a transcription factor with a prominent role in cell homeostasis, can be phosphorylated by the stress kinase p38MAPKat the Thr248/Thr250 motif, while the Thr248Ala/Thr250Ala E2F4 mutant (E2F4DN) triggers multifactorial therapeutic effects in a murine model of Alzheimer’s disease. We hypothesized that the mechanism of action of this therapy relays on the phosphorylation of the Thr248/Thr250 motif under stress conditions, which prevents the homeostatic function of E2F4, while exogenous E2F4DN expression can restore this function. To provide support to this hypothesis, we have focused on genotoxicity induced by camptothecin (CPT) in N2a neuroblastoma-derived neurons, as a paradigm of cell stress followed by cell death. Here we show that, in these cells, p38MAPKbecomes activated 6 h after CPT treatment, followed by E2F4 phosphorylation in the Thr248/Thr250 motif. The effect of this phosphorylation in apoptosis was tested by overexpressing wild-type E2F4 (E2F4WT), its Thr248Glu/Thr250Glu phosphomimetic (E2F4CA) or E2F4DN in CPT-treated N2a neurons, followed by quantification of procaspase-3 cleavage. E2F1, which was used as a positive control, induced a statistically-significant increase of procaspase-3 cleavage 32 h after CPT treatment. This was mimicked by either E2F4WT or E2F4CA, while E2F4DN expression inhibited this effect through a Cited2-dependent mechanism. Pharmacological p38MAPKinhibition prevented cell death by E2F4WT but not by E2F4CA, confirming the requirement of E2F4 phosphorylation for cell death in these cells. We conclude that the phosphorylation of E2F4 facilitates the death of N2a neurons carrying DNA damage, while E2F4DN maintains the homeostatic function of E2F4 under stress conditions.
Pup defence in lactating rats: The underlying neuropeptide signalling and their interactions in the nucleus accumbens shell
Authors: Sanson Alice , Köck Annika , Demarchi Luisa , Ebner Karl , Bosch Oliver J. 
Published: October 2024

AbstractMaternal aggression is a core feature of rodent maternal behaviour to defend their offspring from potential threats and is modulated by corticotropin-releasing factor (CRF) and oxytocin (OXT) systems signalling. Here, we investigated the involvement of those neuropeptide systems in maternal aggression within the nucleus accumbens shell (NAcSh), a central region of the reward and maternal circuits. Infusion of CRF or Urocortin3 (CRF-receptor 2 agonist), as well as an OXT receptor antagonist, reduced maternal aggression, suggesting a role in pup defence. Furthermore, the effects of CRF infusion in the NAcSh continued beyond the maternal defence test (MDT), reducing nursing and increasing self-grooming. Corroborating the involvement of the stress system in maternal aggression, colocalization of CRF and cFos immunoreactive cells were increased in response to the MDT, regardless of pup presence. In addition, MDT exposure increased intra-NAc OXT release in lactating rats, which could be also triggered by local retrodialysis of CRF, but not Urocortin3. However, both ligands of the CRF system elicited dopamine (DA) release in different dynamics.Crh-r1 werepredominantly expressed in the medial NAc on medium-sized spiny neurons (MSN), but also in the rostral part on GABAergic interneurons.Crh-r2were mainly expressed in the rostral NAc and its expression on GABAergic interneurons increased towards the caudal pole. Lastly, we identified CRF-enriched projections to the NAcSh descending from the prefrontal cortex, the amygdala, and the paraventricular thalamus, among others.In conclusion, intra-NAcSh dampened CRF system activity and enhanced OXT system transmission are indispensable for successful pup defence. Any perturbations like increased CRF system signalling might activate compensatory mechanisms to ensure adequate maternal behaviour.
Novel hepatocyte-like liver organoids recapitulate crucial mature hepatic functions
Authors: Ardisasmita A. I. , Joore I. P. , Levy N. , Myszczyszyn A. , Marsee A. , Sinnige T. , Ruiter J. , Ferdinandusse S. , Dudaryeva O. , Gruber E. , Daive V. , Levato R. , Spee B , Verstegen M.M.A. , van der Laan L.J.W. , Nieuwenhuis E. E. S. , Schene I. F. , Fuchs S. A. 
Published: October 2024

AbstractAccurate liver disease modeling and drug toxicity testing still remain challenging as liver cellsin vitropoorly resemble adult hepatocytes, as we previously demonstrated using whole transcriptome and cell identity analysis. To address this, we used our insights into hepatic modeling to develop hepatocyte-like liver organoids (HeLLOs), a novel human organoid model with mature hepatocyte functions superior to existing models. HeLLOs are easily established from (small) healthy or diseased liver tissues and rapidly expanded for an extended period in optimized culture conditions. Transcriptomic and functional analyses revealed that differentiated HeLLOs closely resemble fresh primary human hepatocytes (PHHs) and perform key hepatic functions such as gluconeogenesis, drug metabolism, and bile acid synthesis. We developed a HeLLO-based toxicity assay with higher sensitivity in predicting liver toxicity of known liver-toxic drugs compared to the gold-standard PHHs. By modeling disease-related mechanisms, such as bile acid transport, HeLLOs uncover transport-inhibition toxicity mechanisms of known liver toxic drugs. Single cell sequencing analysis of HeLLOs identified a heterogeneous cluster of cells with cholangiocyte-like and hepatocyte-like cells, overall resembling liver regenerative cells. As such, HeLLOs hold great promise for advancing liver disease modeling and drug testing. To our knowledge, HeLLOs are the best expandable liver model for predicting adverse drug reactions as well as modeling various liver disease mechanisms.
Mechanochemical Patterning Localizes the Organizer of a Luminal Epithelium
Authors: Weevers Sera Lotte , Falconer Alistair D. , Mercker Moritz , Sadeghi Hajar , Ferenc Jaroslav , Ott Albrecht , Oelz Dietmar B. , Marciniak-Czochra Anna , Tsiairis Charisios D. 
Published: October 2024

ABSTRACTThe spontaneous emergence of tissue patterns is often attributed to biochemical reaction-diffusion systems. InHydratissue regeneration, the formation of a Wnt signaling center serves as a well-known example of such a process. However, despite extensive research, a strictly biochemical mechanism for self-organization inHydraremains elusive. In this study, we investigated mechanical stimuli and identified a positive feedback loop between Wnt signaling and tissue stretching. We developed a mathematical model of mechanochemical pattern formation in a closed elastic shell, representing regeneratingHydraepithelial spheroids. Our model explains how mechanical forces drive axis formation and predicts the organizer’s location under various perturbations, providing a more comprehensive understanding of the spatial dynamics involved. Validation by partially confining regenerating tissues showed that the organizer indeed forms in regions with the greatest stretching potential. This work highlights a novel mechanochemical mechanism for luminal epithelium patterning, suggesting that mechanical forces, in addition to biochemical signals, play a crucial role in tissue regeneration and axis specification. Our findings offer broader implications for the role of mechanical forces in tissue organization in various biological systems, opening new avenues for investigating mechanochemical feedback in development and regeneration.
Dynamic imbalances in cell-type specific striatal ensemble activity during visually guided locomotion
Authors: Fearey Brenna , Tong Yuxin , Alexander Andrew , Graham Ben , Howe Mark 
Published: October 2024

AbstractLocomotion is continuously regulated by an animal’s position within an environment relative to goals. Direct and indirect pathway striatal output neurons (dSPNs and iSPNs) influence locomotion, but how their activity is naturally coordinated by changing environments is unknown. We found, in head-fixed mice, that the relative balance of dSPN and iSPN activity was dynamically modulated with respect to position within a visually-guided locomotor trajectory to retrieve reward. Imbalances were present within ensembles of position-tuned SPNs which were sensitive to the visual environment. Our results suggest a model in which competitive imbalances in striatal output are created by learned associations with sensory input to shape context dependent locomotion.