bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning to segment self-generated from externally caused optic flow through sensorimotor mismatch circuits
Authors: Brucklacher Matthias , Pezzulo Giovanni , Mannella Francesco , Galati Gaspare , Pennartz Cyriel M. A. 
Published: November 2023

AbstractEfficient sensory detection requires the capacity to ignore task-irrelevant information, for example when optic flow patterns created by egomotion need to be disentangled from object perception. To investigate how this is achieved in the visual system, predictive coding with sensorimotor mismatch detection is an attractive starting point. Indeed, experimental evidence for sensorimotor mismatch signals in early visual areas exists, but it is not understood how they are integrated into cortical networks that perform input segmentation and categorization. Our model advances a biologically plausible solution by extending predictive coding models with the ability to distinguish self-generated from externally caused optic flow. We first show that a simple three neuron circuit produces experience-dependent sensorimotor mismatch responses, in agreement with calcium imaging data from mice. This microcircuit is then integrated into a neural network with two generative streams. The motor-to-visual stream consists of parallel microcircuits between motor and visual areas and learns to spatially predict optic flow resulting from self-motion. The second stream bidirectionally connects a motion-selective higher visual area (mHVA) to V1, assigning a crucial role to the abundant feedback connections: the maintenance of a generative model of externally caused optic flow. In the model, area mHVA learns to segment moving objects from the background, and facilitates object categorization. Based on shared neurocomputational principles across species, the model also maps onto primate vision. Our work extends the Hebbian predictive coding to sensorimotor settings, in which the agent actively moves - and learns to predict the consequences of its own movements.Significance statementThis research addresses a fundamental challenge in sensory perception: how the brain distinguishes between self-generated and externally caused visual motion. Using a computational model inspired by predictive coding and sensorimotor mismatch detection, the study proposes a biologically plausible solution. The model incorporates a neural microcircuit that generates sensorimotor mismatch responses, aligning with experimental data from mice. This microcircuit is integrated into a neural network with two streams: one predicting self-motion-induced optic flow and another maintaining a generative model for externally caused optic flow. The research advances our understanding of how the brain segments visual input into object and background, shedding light on the neural mechanisms underlying perception and categorization not only in rodents, but also in primates.
The speed of sight: individual variation in critical flicker fusion thresholds
Authors: Haarlem Clinton S. , O’Connell Redmond G. , Mitchell Kevin J. , Jackson Andrew L. 
Published: November 2023

AbstractThe critical flicker fusion threshold is a psychophysical measure commonly used to quantify visual temporal resolution; the fastest rate at which a visual system can discriminate visual signals. Critical flicker fusion thresholds vary substantially among species, reflecting different ecological niches and demands. However, it is unclear how much variation exists in flicker fusion thresholds between healthy individuals of the same species, or how stable this attribute is over time within individuals. In this study, we assessed both inter- and intra-individual variation in critical flicker fusion thresholds in a cohort of healthy human participants within a specific age range, using two common psychophysical methods and three different measurements during each session. The resulting thresholds for each method were highly correlated. We found a between-participant maximum difference of roughly 30 Hz in flicker fusion thresholds and we estimated a 95% prediction interval of 21 Hz. We used random-effects models to compare between- and within-participant variance and found that approximately 80% of variance was due to between-individual differences, and about 10% of the variance originated from within-individual differences over three sessions. Within-individual thresholds did not differ significantly between the three sessions in males, but did in females (P<0.001 for two methods and P<0.05 for one method), indicating that critical flicker fusion thresholds may be more variable in females than in males.
hURAT1Transgenic Mouse Model for Evaluating Targeted Urate-Lowering Agents
Authors: De Gejing , Cai Weiyan , Yang Miyi , Zhao Qinghe , Yi Guohua , Lin Peihui , Chen Apeng 
Published: November 2023

AbstractObjectiveUrate transporter 1 (URAT1), a well-established urate-lowering therapeutic target for hyperuricemia and gout treatment, expresses in the kidney proximal tubule and is responsible for uric acid (UA) reabsorption. However, non-primate animal models currently used in pharmacological studies failed to evaluate URAT1 inhibitor’s effectiveness because their URAT1 has a very low UA affinity compared to human URAT1, resulting in a lag in targeting drug screening and novel therapy development for gout treatment. We established a human URAT1 (hURAT1) transgenic knock-in (KI) mouse model to assess uricosuric agents’ effectiveness and characterize URAT1-caused pathogenesis.MethodsWe generatedhURAT1transgenic mice using CRISPR/Cas9 knock-in technique.mUrat1knockout was achieved by replacing exon 1 coding sequence with a humanSLC22A12CDS-pA cassette. Based on the above transgenic mice, a hyperuricemia model was further established by hypoxanthine administration.ResultsThehURAT1-KI mice successfully expressed hURAT1 protein to the apical side of the kidney proximal tubule epithelium, where a native human URAT1 kidney localization in human body. Upon hypoxanthine challenge, the blood UA level was elevated inhURAT1-KI mice, exhibiting an approximately 37% increase compared towild-type (WT)mice. The elevated blood UA level could be alleviated by hURAT1 inhibitor benzbromarone treatment in thehURAT1-KI mice whereas no response was observed inWTlittermates. Therefore,hURAT1transgenic mice responded well to inhibitors and can be used to evaluate the therapeutic effects.ConclusionThehURAT1-KI hyperuricaemia mouse model would be valuable for preclinical evaluation of urate-lowering agents toward gout treatment and studying UA metabolic complexities in humans.
Invasive traits of freshwater fish database (ITOFF)
Authors: Jessop Aaron , Michalopoulou Anna , Coonan Carolyn , Mazzei Lewis , Sutherland O'Brien Eilidh , Brady Grace , Davison Carly , Gourlay Wayne , Henderson Ethan , Lornie Anna , McCloskey Emily , Ramsay Hannah , Wilson Sophie , Shimadzu Hideyasu , Barbosa Miguel 
Published: November 2023

AbstractAIMSpecies invasions are a major driver of global biodiversity loss, but only a minority of invasions are successful. Evidence suggests that invasive success is linked to life-history traits. Yet, data on invasive success and species’ traits remain fragmented across multiple sources. Here we present the Invasive Traits of Freshwater Fish (ITOFF) database, an interdisciplinary framework that integrates multiple datasets to elucidate the role of life-history traits in shaping invasive success. ITOFF allows seamless access to invasive species data and fosters collaborative actions through knowledge sharing. ITOFF is supported by an innovative web-application that makes complex relationships between invasive and native species accessible to a broad audience. The scientific contribution of ITOFF is illustrated by examining the role of life-history traits and phylogeny in invasion success.LOCATIONGlobal.METHODSGeneralized linear models were used to test the contribution of generation time, trophic level, longevity, and temperature range to invasive success. Through divisive cluster analysis we investigate the role of multiple traits in determining invasive success. Finally, we construct phylogenetic trees to investigate the role of evolutionary history in the invasion process.RESULTSITOFF unifies data for 1917 freshwater fish species representative of invasive species, those species they endanger, and species impacted by invasives but not considered endangered. Invasive species are generally characterized by greater temperature ranges, but are indistinguishable from impacted, endangered, and critically endangered species for the remaining life-history traits. Further, we show that invasive species are generally not distinct from impacted or endangered species when considering multiple traits or phylogeny.MAIN CONCLUSIONSITOFF provides an accessible platform for the improved forecasting of species invasions. ITOFF data shows that classical predictions of life-history traits determining invasive success do not hold amongst freshwater fish species. Forecasting of invasive species must therefore shift towards a wholistic approach encompassing the species and the environment.
MYC–NFATC2 axismaintains cell cycle and mitochondrial function in AML cells
Authors: Patterson S.D. , Massett M.E. , Huang X. , Jørgensen H.G. , Michie A.M. 
Published: November 2023

AbstractAcute myeloid leukaemia (AML) is a clonal haematological malignancy affecting the myeloid lineage with generally poor patient outcomes, owing to the lack of targeted therapies. The histone lysine demethylase 4A (KDM4A) has been established as a novel therapeutic target in AML, due to its selective oncogenic role within leukaemic cells.We identify that the transcription factorNFATC2is a novel binding and transcriptional target of KDM4A in the human AML THP-1 cell line. Further, cytogenetically diverse AML cell lines, including THP-1, were dependent onNFATC2for colony formationin vitro, highlighting a putative novel mechanism of AML oncogenesis.Our study demonstrates thatNFATC2maintenance of cell cycle progression in human AML cells was driven primarily byCCND1. Through RNA-seq and ChIP-seq,NFATC2was shown to bind to the promoter region of genes involved in oxidative phosphorylation and subsequently regulate their gene expression in THP-1 cells. Furthermore, our data show thatNFATC2shares transcriptional targets with the transcription factor c-MYC, withMYCknockdown phenocopyingNFATC2knockdown. These data suggest a novel co-ordinated role forNFATC2andMYCin the maintenance of THP-1 cell function, indicative of a potential means of therapeutic targeting in human AML.Graphical AbstractAcute myeloid leukaemia (AML) cells of diverse cytogenetic backgrounds are dependent onNFATC2for survival; in THP-1 cells,NFATC2is downstream of the epigenetic regulatorKDM4A.NFATC2promotes G1/S phase transition in the cell cycle and oxidative phosphorylation. In addition,NFATC2functions downstream of transcription factorMYC, and maintainsCCND1expression.
Investigating the Association Between Nitrate Dosing and Nitrite Generation by the Human Oral Microbiota in Continuous Culture
Authors: Willmott Thomas , Serrage Hannah J. , Cottrell Elizabeth C. , Humphreys Gavin J. , Myers Jenny , Campbell Paul M. , McBain Andrew J. 
Published: November 2023

AbstractThe generation of nitrite by the oral microbiota is believed to contribute to healthy cardiovascular function, with oral nitrate reduction to nitrite associated with systemic blood pressure regulation. There is the potential to manipulate the composition or activities of the oral microbiota to a higher nitrate-reducing state through nitrate supplementation. The current study examined microbial community composition and enzymatic responses to nitrate supplementation in in sessile oral microbiota grown in continuous culture. Nitrate reductase activity and nitrite concentrations were not significantly different to tongue-derived inocula in model biofilms. These were generally dominated byStreptococcusspp., initially, and a single nitrate supplementation resulted in the increased relative abundance of the nitrate-reducing generaVeillonella, NeisseriaandProteusspp. Nitrite concentrations increased concomitantly and continued to increase throughout oral microbiota development. Continuous nitrate supplementation, over a 7-day period, was similarly associated with an elevated abundance of nitrate-reducing taxa and increased nitrite concentration in the perfusate. In experiments in which the models were established in continuous low or high nitrate environments, there was an initial elevation in nitrate reductase, and nitrite concentrations reached a relatively constant concentration over time similar to the acute nitrate challenge with a similar expansion ofVeillonellaandNeisseria. In summary, we have investigated nitrate metabolism in continuous culture oral biofilms, showing that nitrate addition increases nitrate reductase activity and nitrite concentrations in oral microbiota with the expansion of putatively NaR-producing taxa.ImportanceClinical evidence suggests that blood pressure regulation can be promoted by nitrite generated through the reduction of supplemental dietary nitrate by the oral microbiota. We have utilised oral microbiota models to investigate the mechanisms responsible, demonstrating that nitrate addition increases nitrate reductase activity and nitrite concentrations in oral microbiota with the expansion of nitrate-reducing taxa.
Ice formation and its elimination in cryopreservation of bovine oocytes
Authors: Abdelhady Abdallah W. , Mittan-Moreau David W. , Crane Patrick L. , McLeod Matthew J. , Cheong Soon Hon , Thorne Robert E. 
Published: November 2023

AbstractDamage from ice and potential toxicity of ice-inhibiting cryoprotective agents (CPAs) are key issues in assisted reproduction using cryopreserved oocytes and embryos. We use synchrotron-based time-resolved x-ray diffraction and tools from protein cryocrystallography to characterize ice formation within bovine oocytes after cooling at rates between ∼1000 °C/min and ∼600,000°C /min and during warming at rates between 20,000 and 150,000 °C /min. Maximum crystalline ice diffraction intensity, maximum ice volume, and maximum ice grain size are always observed during warming. All decrease with increasing CPA concentration, consistent with the decreasing free water fraction. With the cooling rates, warming rates and CPA concentrations of current practice, oocytes may show no ice after cooling but always develop substantial ice fractions on warming, and modestly reducing CPA concentrations causes substantial ice to form during cooling. With much larger cooling and warming rates achieved using cryocrystallography tools, oocytes soaked as in current practice remain essentially ice free during both cooling and warming, and when soaked in half-strength CPA solution oocytes remain ice free after cooling and develop small grain ice during warming. These results clarify the roles of cooling, warming, and CPA concentration in generating ice in oocytes, establish the character of ice formed, and suggest that substantial further improvements in warming rates are feasible. Ice formation can be eliminated as a factor affecting post-thaw oocyte viability and development, allowing other deleterious effects of the cryopreservation cycle to be studied, and osmotic stress and CPA toxicity reduced.Significance StatementCryopreservation of oocytes and embryos is critical in assisted reproduction of humans and domestic animals and in preservation of endangered species. Success rates are limited by damage from crystalline ice, toxicity of cryoprotective agents (CPAs), and damage from osmotic stress. Time-resolved x-ray diffraction of bovine oocytes shows that ice forms much more readily during warming than during cooling, that maximum ice fractions always occur during warming, and that the tools and large CPA concentrations of current protocols can at best only prevent ice formation during cooling. Using tools from cryocrystallography that give dramatically larger cooling and warming rates, ice formation can be completely eliminated and required CPA concentrations substantially reduced, expanding the scope for species-specific optimization of post-thaw reproductive outcomes.
The Mouse Epididymal Amyloid Matrix: A Mammalian Counterpart of a Bacterial Biofilm
Authors: Myers Caitlyn , Atkins Georgia Rae , Villarreal Johanna , Sutton R. Bryan , Cornwall Gail A. 
Published: November 2023

AbstractThe mouse epididymis is a long tubule connecting the testis to the vas deferens. Its primary functions are to mature spermatozoa into motile and fertile cells and to protect them from pathogens that ascend the male tract. We previously demonstrated that a functional extracellular amyloid matrix surrounds spermatozoa in the epididymal lumen and has host defense functions; properties not unlike that of an extracellular biofilm that surrounds and protects a bacterial community. Here we show the epididymal amyloid matrix also structurally resembles a biofilm by containing eDNA, eRNA, and mucin-like polysaccharides. Further these structural components exhibit comparable behaviors and perform functions like their counterparts in bacterial biofilms. Our studies suggest that nature has used the ancient building blocks of bacterial biofilms to form an analogous structure that nurtures and protects the mammalian male germline.
Using eDNA to elucidate Silver and Bighead Carp range expansion in two Missouri River tributaries in eastern South Dakota
Authors: LaBrie Lindsey A. P. , Wesner Jeff S. , Britten Hugh B. 
Published: November 2023

AbstractObjectiveThis study used environmental DNA (eDNA) sampling methods to determine the possibility of Bighead CarpHypophthalmichthys nobilis,and Silver CarpH. molitrix, range expansion above barriers to fish movement in two tributaries of the Missouri River in eastern South Dakota.MethodsWe collected water samples above and below two perceived barriers to fish movement: a natural chain of waterfalls in the Big Sioux River and a spillway at the downstream end of a manmade reservoir in the Vermillion River. We used filtration methods to collect invasive carp eDNA from water samples and implemented qPCR techniques to quantify the amount of eDNA in each sample. A total of 213 samples and 38 field blanks were collected over two years (2021/2022).ResultWe detected carp eDNA below both barriers in both years, and above the barrier in the Vermillion River in 2022. The probability of detecting eDNA below the barrier in the Big Sioux River was 51% (95% Credible Interval (CrI): 2 to 97%) and 77% (95% CrI: 8 to 99%) in the Vermillion River. The probability of detecting eDNA above both barriers was significantly smaller: 1% (95% CrI: 0.02 to 24%) for both rivers.ConclusionThe detection of positive samples above the spillway barrier in the Vermillion River provides the first evidence that Bighead and Silver Carp may have expanded their range to habitats upstream of their documented range in eastern South Dakota.Impact StatementThis study demonstrates the utility of using eDNA sampling methods to detect Bighead and Silver Carp in areas of both known and unknown invasive carp presence in smaller tributary streams to the Missouri River.
Comparative and Integrative Single Cell Analysis Reveals New Insights into the Transcriptional Immaturity of Stem Cell-Derived β Cells
Authors: Schmidt Mason D. , Ishahak Matthew , Augsornworawat Punn , Millman Jeffrey R. 
Published: November 2023

SummaryDiabetes cell replacement therapy has the potential to be transformed by human pluripotent stem cell-derived β cells (SC-β cells). However, the precise identity of SC-β cells in relationship to primary fetal and adult β-cells remains unclear. Here, we used single-cell sequencing datasets to characterize the transcriptional identity of islets from in vitro differentiation, fetal islets, and adult islets. Our analysis revealed that SC-β cells share a core β-cell transcriptional identity with human adult and fetal β-cells, however SC-β cells possess a unique transcriptional profile characterized by the persistent expression and activation of progenitor and neural-biased gene networks. These networks are present in SC-β cells, irrespective of the derivation protocol used. Notably, fetal β-cells also exhibit this neural signature at the transcriptional level. Our findings offer insights into the transcriptional identity of SC-β cells and underscore the need for further investigation of the role of neural transcriptional networks in their development.
Neuronal exosomes transport a miRNA/RISC cargo to preserve germline stem cell integrity during energy stress
Authors: Wong Christopher , Jurczak Elena M. , Roy Richard 
Published: November 2023

AbstractDuring periods of nutrient scarcity, many animals undergo germline quiescence to preserve reproductive capacity, and neurons are often necessary for this adaptation. We show here that starvation causes the release of neuronal miRNA/Argonaute-loaded exosomes following AMPK-regulated trafficking changes within serotonergic neurons. This neuron-to-germ line communication is independent of classical serotonergic neurotransmission, but instead relies on endosome-derived vesicles that carry a pro-quiescent miRNA cargo to modify germline gene expression. Using a miRNA activity sensor, we show that neuronally-expressed miRNAs can extinguish the expression of germline-mRNA targets in an exosome-dependent manner. Our findings demonstrate how an adaptive neuronal response can change gene expression at a distance by re-directing intracellular trafficking to release neuronal exosomes with specific miRNA cargos capable of tracking to their appropriate destinations.One Sentence SummaryNeurons release miRNA Argonaute-containing exosomes to establish germline stem cell quiescence in response to energy stress.
Rapid and Highly Sensitive Detection of Fentanyl and its Analogs by a Novel Chemiluminescence Immunoassay
Authors: Zhao Jiang-yang , Uddin Mezbah , Unsihuay Daisy , Butler William , Xia Terrance W. , Xu Jayson Z. , Jannetto Paul J. , Wang Ping , Xia Xiaofeng 
Published: November 2023

AbstractA highly sensitive immunoassay with sub-picogram limit of detection for fentanyl and a wide range of fentanyl analogs has been developed, using a novel high affinity antibody fused with NanoLuc, a small-size luciferase that can emit strong and stable luminescence. When applied to unaltered clinical human urine samples, the assay has sub-picogram limit of detection for fentanyl, with results fully concordant with gold standard liquid chromatography-mass spectrometry. When applied to environmental samples, the assay can detect as low as 0.25 pg fentanyl per inch2environment surface. Assay turn-around-time is less than 1 hour, with inexpensive equipment needed and potential for high throughput automation or in-field screening. This novel assay has broad potential applications in clinical, environmental, occupational and forensic scenarios by detecting trace amount of fentanyl and its analogs to keep frontline workers safe.