bluuebunny/crossref_metadata_2025_split huggingface dataset:
BPTF cooperates with MYCN and MYC to link neuroblastoma cell cycle control to epigenetic cellular states
Authors: Felipe Irene , Martínez-de-Villarreal Jaime , Patel Khushbu , Martínez-Torrecuadrada Jorge , Grossmann Liron D. , Roncador Giovanna , Cubells Mariona , Farrell Alvin , Kendsersky Nathan , Sabroso-Lasa Sergio , Sancho-Temiño Lucía , Torres Kyabeth , Martinez Daniel , Perez Javier Muñoz , García Fernando , Pogoriler Jenny , Moreno Lucas , Maris John M. , Real Francisco X. 
Published: February 2024

AbstractThe nucleosome remodeling factor BPTF is required for the deployment of the MYC-driven transcriptional program. Deletion of oneBptfallele delays tumor progression in mouse models of pancreatic cancer and lymphoma. In neuroblastoma, MYCN cooperates with the transcriptional core regulatory circuitry (CRC). HighBPTFlevels are associated with high-risk features and decreased survival. BPTF depletion results in a dramatic decrease of cell proliferation. Bulk RNA-seq, single-cell sequencing, and tissue microarrays reveal a positive correlation ofBPTFand CRC transcription factor expression. Immunoprecipitation/mass spectrometry shows that BPTF interacts with MYCN and the CRC proteins. Genome-wide distribution analysis of BPTF and CRC in neuroblastoma reveals a dual role for BPTF: 1) it co-localizes with MYCN/MYC at the promoter of genes involved in cell cycle and 2) it co-localizes with the CRC at super-enhancers to regulate cell identity. The critical role of BPTF across neuroblastoma subtypes supports its relevance as a therapeutic target.
Profiling IOP-responsive genes in anterior and posterior ocular tissues in the rat CEI glaucoma model
Authors: Lozano Diana C. , Yang Yong-Feng , Cepurna William O. , Smoody Barbara F. , Ing Eliesa , Morrison John C. , Keller Kate E. 
Published: February 2024

AbstractPurposeThe rat Controlled Elevation of Intraocular pressure (CEI) model allows study ofin vivoresponses to defined intraocular pressures (IOP). In this study, we use Nanostring technology to investigatein vivoIOP-related gene responses in the trabecular meshwork (TM) and optic nerve head (ONH) simultaneously from the same animals.MethodsMale and female rats (N=35) were subject to CEI for 8-hours at pressures simulating mean, daytime normotensive rat IOP (CEI-20), or 2.5x IOP (CEI-50). Naïve animals, receiving no anesthesia or surgical interventions, served as controls. Immediately after CEI, TM and ONH tissues were dissected, RNA isolated, and samples were analyzed with a Nanostring panel containing 770 genes. Post-processing, raw count data were uploaded to Rosalind® for differential gene expression analyses.ResultsFor the TM, 45 IOP-related genes were significant in the “CEI-50 vs. CEI-20” and “CEI-50 vs. naïve” comparisons, with 15 genes common to both comparisons. Bioinformatics analysis identified Notch and TGFβ pathways to be the most up- and down-regulated KEGG pathways, respectively. For ONH, 22 significantly regulated genes were identified in the “CEI-50 vs. naïve” comparison. Pathway analysis identified ‘defense response’ and ‘immune response’ as two significantly upregulated biological process pathways.ConclusionsThis study demonstrates the ability to assay IOP-responsive genes in both TM and ONH tissues simultaneously. In the TM, downregulation of TGFβ pathway genes suggest that TM responses may prevent TGFβ-induced extracellular matrix synthesis. For ONH, the initial response to elevated IOP may be protective, with astrocytes playing a key role in these gene responses.
DNA barcoding affirms the presence of invasiveParachanna obscuraand new records of some species in the Mweru-Luapula fishery
Authors: Seemani Bornwell , Katongo Cyprian , Bloomer Paulette , Klopper Arrie W. , Oosthuizen Carel J. 
Published: February 2024

AbstractDNA barcoding has recently been instrumental in identifying both invasive and undetected species in aquatic environments. This study aimed at analysing collected fish fin clips to ascertain the identity of native species and theParachannaspecies that have invaded the Mweru-Luapula (ML) fishery of Zambia. The identification process was carried out through field phenotypic analysis using species guides and DNA barcoding, with the mitochondrial DNA (mtDNA) cytochrome C oxidase 1 (COI) gene fragment. Of the 28 specimens for which DNA was successfully PCR amplified, five matched the reference sequences of species and 22 matched the reference sequences of genera on the NCBI GenBank. Five unexpected species, namelyOreochromis niloticus, Coptodon zillii, Mormyrus kannume, Thoracochromis buysiandTylochromis polylepiswere identified. The study further affirmed the presence of invasiveParachanna obscurain the fishery and its interconnected water bodies.Parachanna obscurainvaded the fishery through annual flooding from aquacultural facilities in the Democratic Republic of Congo (DRC). There is a need to investigate this invasion further by using large sample sizes and also by applying the gonadosomatic index (GSI) to determine invasive species occupancy and impact on native species throughout the fishery. This study provides a platform for further detailed taxonomic verification and species inventory of the entire ML fishery. This will facilitate the development of a viable and sustainable strategy to appropriately curb the impact of invasive species, and will thus contribute to the conservation of the ML aquatic biodiversity.
Integrated transcriptomic analysis of human induced pluripotent stem cell-derived osteogenic differentiation reveals a regulatory role of KLF16
Authors: Ru Ying , Ma Meng , Zhou Xianxiao , Kriti Divya , Cohen Ninette , D’Souza Sunita , Schaniel Christoph , Motch Perrine Susan M. , Kuo Sharon , Pichurin Oksana , Pinto Dalila , Housman Genevieve , Holmes Greg , Schadt Eric , van Bakel Harm , Zhang Bin , Jabs Ethylin Wang , Wu Meng 
Published: February 2024

AbstractOsteogenic differentiation is essential for bone development, metabolism, and repair; however, the underlying regulatory relationships among genes remain poorly understood. To elucidate the transcriptomic changes and identify novel regulatory genes involved in osteogenic differentiation, we differentiated mesenchymal stem cells (MSCs) derived from 20 human iPSC lines into preosteoblasts (preOBs) and osteoblasts (OBs). We then performed transcriptome profiling of MSCs, preOBs and OBs. The iPSC-derived MSCs and OBs showed similar transcriptome profiles to those of primary human MSCs and OBs, respectively. Differential gene expression analysis revealed global changes in the transcriptomes from MSCs to preOBs, and then to OBs, including the differential expression of 840 genes encoding transcription factors (TFs). TF regulatory network analysis uncovered a network comprising 451 TFs, organized into five interactive modules. Multiscale embedded gene co-expression network analysis (MEGENA) identified gene co-expression modules and key network regulators (KNRs). From these analyses,KLF16emerged as an important TF in osteogenic differentiation. We demonstrate that overexpression ofKlf16in vitro inhibited osteogenic differentiation and mineralization, whileKlf16+/-mice exhibited increased bone mineral density, trabecular number, and cortical bone area. Our study underscores the complexity of osteogenic differentiation and identifies novel regulatory genes such asKLF16, which plays an inhibitory role in osteogenic differentiation both in vitro and in vivo.
Impaired drainage through capillary-venous networks contributes to age-related white matter loss
Authors: Stamenkovic Stefan , Schmid Franca , Weitermann Nicolas , Takasaki Kevin , Bonney Stephanie K. , Sosa Maria J. , Li Yuandong , Bennett Hannah C. , Kim Yongsoo , Waters Jack , Shih Andy Y. 
Published: February 2024

ABSTRACTThe gradual loss of cerebral white matter contributes to cognitive decline during aging. However, microvascular networks that support the metabolic demands of white matter remain poorly defined. We usedin vivodeep multi-photon imaging to characterize microvascular networks that perfuse cortical layer 6 and corpus callosum, a highly studied region of white matter in the mouse brain. We show that these deep tissues are exclusively drained by sparse and wide-reaching venules, termed principal cortical venules, which mirror vascular architecture at the human cortical-U fiber interface. During aging, capillary networks draining into deep branches of principal cortical venules are selectively constricted, reduced in density, and diminished in pericyte numbers. This causes hypo-perfusion in deep tissues, and correlates with gliosis and demyelination, whereas superficial tissues become relatively hyper-perfused. Thus, age-related impairment of capillary-venular drainage is a key vascular deficit that contributes to the unique vulnerability of cerebral white matter during brain aging.
DNA methylation-dependent and -independent binding of CDX2 directs activation of distinct developmental and homeostatic genes
Authors: Lorzadeh Alireza , Ye George , Sharma Sweta , Jadhav Unmesh 
Published: February 2024

AbstractPrecise spatiotemporal and cell type-specific gene expression is essential for proper tissue development and function. Transcription factors (TFs) guide this process by binding to developmental stage-specific targets and establishing an appropriate enhancer landscape. In turn, DNA and chromatin modifications direct the genomic binding of TFs. However, how TFs navigate various chromatin features and selectively bind a small portion of the millions of possible genomic target loci is still not well understood. Here we show that Cdx2 - a pioneer TF that binds distinct targets in developing versus adult intestinal epithelial cells - has a preferential affinity for a non-canonical CpG-containing motifin vivo. A higher frequency of this motif at embryonic and fetal Cdx2 target loci and the specifically methylated state of the CpG during development allows selective Cdx2 binding and activation of developmental enhancers and linked genes. Conversely, demethylation at these enhancers prohibits ectopic Cdx2 binding in adult cells, where Cdx2 binds its canonical motif without a CpG. This differential Cdx2 binding allows for corecruitment of Ctcf and Hnf4, facilitating the establishment of intestinal superenhancers during development and enhancers mediating adult homeostatic functions, respectively. Induced gain of DNA methylation in the adult mouse epithelium or cultured cells causes ectopic recruitment of Cdx2 to the developmental target loci and facilitates cobinding of the partner TFs. Together, our results demonstrate that the differential CpG motif requirements for Cdx2 binding to developmental versus adult target sites allow it to navigate different DNA methylation profiles and activate cell type-specific genes at appropriate times.Graphical Abstract
Graph-based Nanopore Adaptive Sampling with GNASTy enables sensitive pneumococcal serotyping in complex samples
Authors: Horsfield Samuel T. , Fok Basil , Fu Yuhan , Turner Paul , Lees John A. , Croucher Nicholas J. 
Published: February 2024

AbstractSerotype surveillance ofStreptococcus pneumoniae(the pneumococcus) is critical for understanding the effectiveness of current vaccination strategies. However, existing methods for serotyping are limited in their ability to identify co-carriage of multiple pneumococci and detect novel serotypes. To develop a scalable and portable serotyping method that overcomes these challenges, we employed Nanopore Adaptive Sampling (NAS), an on-sequencer enrichment method which selects for target DNA in real-time, for direct detection ofS. pneumoniaein complex samples. Whereas NAS targeting the wholeS. pneumoniaegenome was ineffective in the presence of non-pathogenic streptococci, the method was both specific and sensitive when targeting the capsular biosynthetic locus (CBL), the operon that determinesS. pneumoniaeserotype. NAS significantly improved coverage and yield of the CBL relative to sequencing without NAS, and accurately quantified the relative prevalence of serotypes in samples representing co-carriage. To maximise the sensitivity of NAS to detect novel serotypes, we developed and benchmarked a new pangenome-graph algorithm, named GNASTy. We show that GNASTy outperforms the current NAS implementation, which is based on linear genome alignment, when a sample contains a serotype absent from the database of targeted sequences. The methods developed in this work provide an improved approach for novel serotype discovery and routineS. pneumoniaesurveillance that is fast, accurate and feasible in low resource settings. GNASTy therefore has the potential to increase the density and coverage of global pneumococcal surveillance.One sentence summaryPangenome graph-based Nanopore Adaptive Sampling, presented in our tool GNASTy, is a sensitive, portable and cost-effective method forStreptococcus pneumoniaesurveillance.
The impact of face masks on face-to-face neural tracking of speech: auditory and visual obstacles
Authors: Fantoni M. , Federici A. , Camponogara I. , Handjaras G. , Martinelli A. , Bednaya E. , Ricciardi E. , Pavani F. , Bottari D. 
Published: February 2024

AbstractFace masks provide fundamental protection against the transmission of respiratory viruses but hamper communication. We estimated auditory and visual obstacles generated by face masks on communication by measuring the neural tracking of face-to-face speech. To this end, we recorded the EEG while participants were exposed to naturalistic audio-visual speech, embedded in multi-talker noise, in three contexts: (i) no-mask (audio-visual information was fully available), (ii) virtual mask (occluded lips, but intact audio), and (iii) real mask (occluded lips and degraded audio). The neural tracking of lip movements and the sound envelope of speech was measured through backward modeling, that is, by reconstructing stimulus properties from neural activity. Behaviorally, face masks increased listening -phonological-errors in speech content retrieval and perceived listening difficulty. At the neural level, we observed that the occlusion of the mouth abolished lip tracking and dampened neural tracking of the speech envelope at the earliest processing stages. Degraded acoustic information due to face mask filtering altered neural tracking at later processing stages instead. Finally, a consistent link emerged between the increment of listening perceived difficulty and the drop in reconstruction performance of speech envelope when attending to a speaker wearing a face mask. Results clearly dissociated the visual and auditory impacts of face masks on face-to-face neural tracking of speech. While face masks hampered the ability to predict and integrate audio-visual speech, the auditory filter generated by face masks impacted the neural processing stages typically associated with auditory selective attention. The link between perceived difficulty and neural tracking drop provided evidence of a major impact of face masks on the metacognitive levels subtending speech processing.
Age-dependent dynamics of neuronal VAPBALSinclusions in the adult brain
Authors: Thulasidharan Aparna , Garg Lovleen , Tendulkar Shweta , Ratnaparkhi Girish S 
Published: February 2024

ABSTRACTAmyotrophic Lateral Sclerosis (ALS) is a relentlessly progressive and fatal disease, caused by the degeneration of upper and lower motor neurons within the brain and spinal cord in the ageing human. The dying neurons contain cytoplasmic inclusions linked to the onset and progression of the disease. Here, we use aDrosophilamodel ofALS8 (VAPP58S)to understand the modulation of these inclusions in the ageing adult brain.The adultVAPP58Sfly shows progressive deterioration in motor function till its demise 25 days post-eclosion. The density of VAPP58S-positive brain inclusions is stable for 5-15 days of age. In contrast, adding a single copy ofVAPWTto theVAPP58Sanimal leads to a large decrease in inclusion density with concomitant rescue of motor function and lifespan. ER stress, a contributing factor in disease, shows reduction with ageing for the disease model. Autophagy, rather than the Ubiquitin Proteasome system, is the dominant mechanism for aggregate clearance.We explored the ability ofDrosophilaValosin-containing protein (VCP/TER94), theALS14locus, which is involved in cellular protein clearance, to regulate age-dependent aggregation. Contrary to expectation,TER94overexpression increased VAPP58Spunctae density, while its knockdown led to enhanced clearance. Expression of a dominant positive allele,TER94R152H,further stabilised VAPP58Spuncta, cementing roles for anALS8-ALS14axis. Our results are explained by a mechanism where autophagy is modulated byTER94knockdown.Our study sheds light on the complex regulatory events involved in the neuronal maintenance of ALS8 aggregates, suggesting a context-dependent switch between proteasomal and autophagy-based mechanisms as the larvae develop into an adult. A deeper understanding of the nucleation and clearance of the inclusions, which affect cellular stress and function, is essential for understanding the initiation and progression of ALS.
Modeling Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids using microglia-sufficient brain organoids
Authors: Wong Wei Jie , Zhu Yi Wen , Wang Hai Ting , Qian Jia Wen , Li Ziyi , Li Song , Liu Zhao Yuan , Guo Wei , Zhang Shuang Yan , Su Bing , He Fang Ping , Wang Kang , Ginhoux Florent 
Published: February 2024

AbstractHereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare, fatal, adult-onset neurodegenerative disease that is most often caused by mutations affecting the Colony Stimulating factor-1 Receptor (CSF-1R). To understand how CSF-1R-mutation affects human microglia – the specialized brain-resident macrophages of the central nervous system – and the downstream consequences for neuronal cells, we used a macrophage and forebrain organoid co-culture system based on induced pluripotent stem cells generated from two patients with HDLS, withCSF-1Rgene-corrected isogenic organoids as controls. Macrophages derived from iPSC (iMacs) of patients exhibited a metabolic shift towards the glycolytic pathway and reduced CSF-1 sensitivity, which was associated with higher levels of IL-1β production and an activated inflammatory phenotype. Single-cell RNA sequencing revealed that iMacs adopt a reactive state that leads to impaired regulation of neuronal cell populations in organoid cultures, thereby identifying microglial dysregulation and specifically IL-1β production as key contributors to the degenerative neuro-environment in HDLS.
Continuous Bump Attractor Networks Require Explicit Error Coding for Gain Recalibration
Authors: Secer Gorkem , Knierim James J. , Cowan Noah J. 
Published: February 2024

AbstractRepresentations of continuous variables are crucial to create internal models of the external world. A prevailing model of how the brain maintains these representations is given by continuous bump attractor networks (CBANs) in a broad range of brain functions across different areas, such as spatial navigation in hippocampal/entorhinal circuits and working memory in prefrontal cortex. Through recurrent connections, a CBAN maintains a persistent activity bump, whose peak location can vary along a neural space, corresponding to different values of a continuous variable. To track the value of a continuous variable changing over time, a CBAN updates the location of its activity bump based on inputs that encode the changes in the continuous variable (e.g., movement velocity in the case of spatial navigation)—a process akin to mathematical integration. This integration process is not perfect and accumulates error over time. For error correction, CBANs can use additional inputs providing ground-truth information about the continuous variable’s correct value (e.g., visual landmarks for spatial navigation). These inputs enable the network dynamics to automatically correct any representation error. Recent experimental work on hippocampal place cells has shown that, beyond correcting errors, ground-truth inputs also fine-tune the gain of the integration process, a crucial factor that links the change in the continuous variable to the updating of the activity bump’s location. However, existing CBAN models lack this plasticity, offering no insights into the neural mechanisms and representations involved in the recalibration of the integration gain. In this paper, we explore this gap by using a ring attractor network, a specific type of CBAN, to model the experimental conditions that demonstrated gain recalibration in hippocampal place cells. Our analysis reveals the necessary conditions for neural mechanisms behind gain recalibration within a CBAN. Unlike error correction, which occurs through network dynamics based on ground-truth inputs, gain recalibration requires an additional neural signal that explicitly encodes the error in the network’s representation via a rate code. Finally, we propose a modified ring attractor network as an example CBAN model that verifies our theoretical findings. Combining an error-rate code with Hebbian synaptic plasticity, this model achieves recalibration of integration gain in a CBAN, ensuring accurate representation for continuous variables.
Effects of Turbidity and Habitat Complexity on the Foraging Behavior of the Black Bullhead (Ameiurus melas)
Authors: Preiszner Bálint , Szolnoki Anna , Czeglédi István , Erős Tibor 
Published: February 2024

AbstractThe role of vertebrate scavengers in nutrient flow of aquatic ecosystems has recently been emphasized. Evidence is accumulating that scavenging is an alternative tactic for certain predatory fish, but their foraging choices between scavenging and predation under varying environmental conditions have not been studied. In this experiment, we presented black bullheads,Ameiurus melas(Rafinesque, 1820), with both live and carcass prey of tubenose gobies,Proterorhinus semilunaris(Heckel, 1837), in aquaria with varying levels of turbidity and habitat complexity. Our findings revealed that black bullheads exhibit higher consumption of carcass prey in complex habitat and clear water condition. We also provide evidence of the active predatory behavior displayed by black bullheads, as a greater consumption of live prey was observed in simple habitat and turbid water. We did not find any relationship between individual exploratory behavior and the choice between carcass and live prey in black bullheads. Our results suggest that the choice between scavenging versus predatory foraging strategy under varying environmental conditions is influenced by the behavior of both consumer and prey. The ability of black bullheads to adapt their foraging strategy in different environments may contribute to their widespread success as an invasive species.