bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultraslow serotonin oscillations in the hippocampus delineate substates across NREM and waking
Authors: Cooper Claire , Parthier Daniel , Sibille Jérémie , Tukker John , Tritsch Nicolas X. , Schmitz Dietmar 
Published: July 2024

AbstractBeyond the vast array of functional roles attributed to serotonin (5-HT) in the brain, changes in 5-HT levels have been shown to accompany changes in behavioral states, including WAKE, NREM and REM sleep. Whether 5-HT dynamics at shorter time scales can be seen to delineate substates within these larger brain states remains an open question. Here, we performed simultaneous recordings of extracellular 5-HT using a recently-developed G Protein–Coupled Receptor-Activation–Based 5-HT sensor (GRAB5-HT3.0) and local field potential (LFP) in the hippocampal CA1, which revealed the presence of prominent ultraslow (<0.05 Hz) 5-HT oscillations both during NREM and WAKE states. Interestingly, the phase of these ultraslow 5-HT oscillations was found to distinguish substates both within and across larger behavioral states. Hippocampal ripples occurred preferentially on the falling phase of ultraslow 5-HT oscillations during both NREM and WAKE, with higher power ripples concentrating near the peak specifically during NREM. By contrast, hippocampal-cortical coherence was strongest and microarousals and EMG peaks were most prevalent during the rising phase in both wake and NREM. Overall, ultraslow 5-HT oscillations delineate substates within the larger behavioral states of NREM and WAKE, thus potentially temporally segregating internal memory consolidation processes from arousal-related functions.
Influence of asymmetric microchannels in the structure and function of engineered neuronal circuits
Authors: Mateus JC , Melo P , Aroso M , Charlot B , Aguiar P 
Published: July 2024

ABSTRACTUnderstanding the intricate structure-function relationships of neuronal circuits is crucial for unraveling how the brain sustains efficient information transfer. In specific brain regions, like the hippocampus, neurons are organized in layers and form unidirectional connectivity, which is thought to help ensure controlled signal flow and information processing. In recent years, researchers have tried emulating these structural principles by providing cultured neurons with asymmetric environmental cues, namely microfluidics’ microchannels that promote directed axonal growth. Even though a few reports have claimed achieving unidirectional connectivity ofin vitroneuronal circuits, given the lack of functional characterization, whether this structural connectivity correlates with functional connectivity remains unknown.We have replicated and tested the performance of asymmetric microchannel designs previously reported in the literature to be successful in the promotion of directed axonal growth, as well as other custom variations. A new variation of “Arrowhead”, termed “Rams”, was the best-performing motif with a ∼76% probability per microchannel of allowing strictly unidirectional connections at 14 days in vitro. Importantly, we assessed the functional implications of these different asymmetric microchannel designs. For this purpose, we combined custom microfluidics with microelectrode array (MEA) technology to record the electrophysiological activity of two segregated populations of hippocampal neurons (“Source” and “Target”). This functional characterization revealed that up to ∼94% of the spiking activity recorded along microchannels with the “Rams” motif propagates towards the “Target” population. Moreover, our results indicate that these engineered circuits also tended to exhibit network-level synchronizations with defined directionality.Overall, this characterization of the structure-function relationships promoted by asymmetric microchannels has the potential to provide insights into how neuronal circuits use specific network architectures for effective computations. Moreover, the here-developed devices and approaches may be used in a wide range of applications, such as disease modeling or preclinical drug screening.
Are cell length and volume interchangeable in cell cycle analysis?
Authors: Kar Prathitha , Amir Ariel 
Published: July 2024

AbstractCell length has been used as a proxy for cell size in cell cycle modeling studies. A previous study, however, brought into question the validity of this assumption, noting that correlations between cell lengths can be different from those involving cell volume if cell width fluctuations are taken into account. If cell volume is regulated, data analysis involving cell lengths will lead to an incorrect inference of the cell size control mechanism. We used conditional correlation of length variables conditioned upon radius variables to elucidate the underlying volume control mechanism. Using the conditional correlation on previous mother machine datasets measuring lengths at birth and division, and the cell radius for multiple cells, we find that the cell volume control strategy is consistent with an adder model. Further, using the conditional correlation, we conclude that measurement noise constitutes a significant portion of the radius variability in the experimental datasets. To conclude, cell length and cell volume can often be used interchangeably owing to small cell width fluctuations.
Genomic insights into red squirrels in Scotland reveals loss of heterozygosity associated with extreme founder effects
Authors: Marr Melissa M. , Humble Emily , Lurz Peter W. W. , Wilson Liam A. , Milne Elspeth , Beckmann Katie M. , Schoenebeck Jeffrey , Fung Uva-Yu-Yan , Kitchener Andrew C. , Kortland Kenny , Edwards Colin , Ogden Rob 
Published: July 2024

AbstractRemnant populations of endangered species often have complex demographic histories associated with human impact. This can present challenges for conservation as the genetic status of these populations are often a-typical of natural populations, and may require bespoke management. The Eurasian red squirrel,Sciurus vulgaris (L., 1758), is endangered in the UK. Scotland represents a key stronghold, but Scottish populations have been subjected to intense anthropogenic influence, including wide-spread extirpations, reintroductions and competition from an invasive species. This study examined the genetic legacy of these events through whole genome resequencing of 106 red squirrels. Using SNP and genotype likelihood datasets, previously undetected population structure and patterns of gene-flow were uncovered. One off-shore island, three mainland Scottish populations, and a key east-coast migration corridor were observed. An abrupt historical population bottleneck related to extreme founder effects has led to a severe and prolonged depression in genome-wide heterozygosity, which is amongst the lowest reported for any species. Current designated red squirrel conservation stronghold locations do not encompass all existing diversity. These findings highlight the genetic legacies of past anthropogenic influence on long-term diversity in endangered taxa. Continuing management interventions and regular genetic monitoring are recommended to safeguard and improve future diversity.
STRPsearch: fast detection of structured tandem repeat proteins
Authors: Mozaffari Soroush , Arrías Paula Nazarena , Clementel Damiano , Piovesan Damiano , Ferrari Carlo , Tosatto Silvio C. E. , Monzon Alexander Miguel 
Published: July 2024

AbstractMotivationState-of-the-art prediction methods are generating millions of publicly available protein structures. Structured Tandem Repeats Proteins (STRPs) constitute a subclass of tandem repeats characterized by repetitive structural motifs. STRPs exhibit distinct propensities for secondary structure and form regular tertiary structures, often comprising large molecular assemblies. They can perform important and diverse biological functions due to their highly degenerated sequences, which maintain a similar structure while displaying a variable number of repeat units. This suggests a disconnection between structural size and protein function. However, automatic detection of STRPs remains challenging with current state-of-the-art tools due to their lack of accuracy and long execution times, hindering their application on large datasets. In most cases, manual curation is the most accurate method for detecting and classifying them, making it impossible to inspect millions of structures.ResultsWe present STRPsearch, a novel computational tool for rapid identification, classification, and mapping of STRPs. Leveraging the manually curated entries in RepeatsDB as the known conformational space of the STRPs, STRPsearch utilizes the latest advancements in structural alignment techniques for a fast and accurate detection of repeated structural motifs in protein structures, followed by an innovative approach to map units and insertions through the generation of TM-score graphs. STRPsearch can serve researchers in structural bioinformatics and protein science as an efficient and practical tool for analysis and detection of STRPs.Availability and implementationSTRPsearch is coded in Python, all the scripts and the associated documentation are available athttps://github.com/BioComputingUP/STRPsearch.Contactalexander.monzon@unipd.it,silvio.tosatto@unipd.itSupplementary informationSupplementary data are available..
Search for candidate substances from the spiny red gurnardChelidonichthys spinosus, as novel food additives that color cultivated meat red
Authors: Shimada Eriko , Tsuruwaka Yusuke 
Published: July 2024

AbstractThe spiny red gurnardChelidonichthys spinosusis a fish with a unique evolution of brightly colored fins consisting of various colors. In Japan, the fish is also used as an ingredient for fish paste products such as fish cake, because of its small edible portion in the processed food industry.We previously reported on the preparation of “sashimi” in the field of cellular agriculture. In this study, we attempted to explore for cell types suitable for “surimi” or fish paste products and to establish a culture method. In particular, we focused on the development of raw materials for cultivated meat containing pigment cells from edible fish, the spiny red gurnard. As a result, migratory cells were succeeded to be observed from a portion of the fish fin by the migration method. Three types of cells were found in the migrating cells: epithelial-like, fibroblast-like, and those cells containing pigment. Five or more passages of culture were possible, suggesting that the cells could be used as one of the raw materials for cultivated meat surimi in the future. The pigmented cells in particular are expected to be a naturally occurring material that can be used to color surimi.
Transposable element accumulation drives genome size increase inHylesia metabus(Lepidoptera: Saturniidae), an urticating moth species from South America
Authors: Perrier Charles , Allio Rémi , Legeai Fabrice , Gautier Mathieu , Bénéluz Frédéric , Marande William , Theron Anthony , Rodde Nathalie , Herrera Melfran , Saune Laure , Parrinello Hugues , Mcclure Melanie , Arias Mónica 
Published: July 2024

AbstractWe present the first nuclear genome assembly and a complete mitogenome forHylesia metabus(Arthropoda; Insecta; Lepidoptera; Saturniidae). The assembled nuclear genome sequence is 1,271 Mb long, which is among the 10 largest lepidopteran genome assemblies published to date. It is scaffolded in 31 pseudo chromosomes, has a BUSCO score of 99.5%, and has a highly conserved synteny compared to phylogenetically close species. Repetitive elements make up 67% of the nuclear genome and are mainly located in intergenic regions, among which LINEs were predominant, with CR1-Zenon being the most abundant. Phylogenetic and comparative analyses ofH. metabusassembly and 17 additional Saturniidae and Sphingidae assemblies suggested that an accumulation of repetitive elements likely led to the increased size ofH. metabus’genome. Gene annotation using Helixer identified 26,122 transcripts. The Z scaffold was identified using both a synteny analysis and variations of coverage for two resequenced male and femaleH. metabus. TheH. metabusnuclear genome and mitogenome assemblies can be found and browsed on the BIPAA website and constitute useful resources for future population and comparative genomics studies.
How to choose the optimal RNA-Seq library characteristics for alternative splicing analysis
Authors: Ladwig Annika , Klostermann Melina , Zarnack Kathi 
Published: July 2024

AbstractAlternative splicing (AS) is a key layer of regulation in eukaryotic gene expression that is investigated in all areas of life sciences. Differences in AS between conditions can be quantified from transcriptome-wide short-read RNA sequencing (RNA-Seq) data with designated computational tools. However, not all short-read RNA-Seq data are equally suited for AS analysis. Here, we perform an exemplary AS analysis to showcase the impact of the RNA-Seq library characteristics on the obtained results. Using three standard ENCODE datasets with widespread AS changes, we modulate read length, read depth and the number of replicates and compare their influence on the detection, quantification and classification of AS events with the state-of-the-art AS algorithm MAJIQ. We find that longer reads and a higher read depth are the most effective measures to improve the sensitivity and precision of the analysis. From our results, we provide a recommendation on how to best choose the short-read RNA-Seq library specifications for an AS analysis.
Developing a Soft Micropatterned Substrate to Enhance Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs)
Authors: Maaref Yasaman , Jannati Shayan , Akbari Mohsen , Chiao Mu , Tibbits Glen F 
Published: July 2024

ABSTRACTHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer numerous advantages as a biological model, yet their inherent immaturity compared to adult cardiomyocytes poses significant limitations. This study addresses hiPSC-CM immaturity by introducing a novel physiologically relevant micropatterned substrate for long-term culture and maturation. A novel microfabrication technique combining laser etching and casting creates a micropatterned polydimethylsiloxane (PDMS) substrate with varying stiffness, from 2 to 50 kPa, mimicking healthy and fibrotic cardiac tissue, respectively. Platinum electrodes integrated into the cell culture chamber enabled pacing of cells at various frequencies. Subsequently, cells were transferred to the incubator for time-course analysis, ensuring contamination-free conditions. Cell contractility, cytosolic Ca2+transient, sarcomere orientation, distribution, and nucleus aspect ratio are analyzed in a 2D hiPSC-CM monolayer up to 90 days post-replating in relation to substrate micropattern dimensions. Culturing hiPSC-CMs for three weeks on a micropatterned PDMS substrate (2.5-5 µm deep, 20 µm center-to-center spacing of grooves, 2-5 kPa stiffness) emerges as optimal for cardiomyocyte alignment, nucleus aspect ratio, contractility, and cytosolic Ca2+transient. The study provides significant insights into substrate stiffness effects on hiPSC-CM contractility and Ca2+transient at immature and mature states. Maximum contractility and fastest Ca2+transient kinetics occur in mature hiPSC-CMs cultured for two to four weeks, with the optimum at three weeks, on a soft micropatterned PDMS substrate. This new substrate offers a promising platform for disease modeling and therapeutic interventions.
Kidney mRNA-protein expression correlation: What can we learn from the Human Protein Atlas?
Authors: Acoba Dianne , Reznichenko Anna 
Published: July 2024

ABSTRACTThe Human Protein Atlas (HPA), with more than 10 million immunohistochemical images showing tissue- and cell-specific protein expression levels and subcellular localization information, is widely used in kidney research. The HPA contains comprehensive data on multi-tissue transcript and protein abundance, allowing for comparisons across tissues. However, while visual and intuitive to interpret, immunohistochemistry is limited by its semi-quantitative nature. This can lead to mismatches in protein expression measurements across different platforms. We performed a comparison of the HPA’s kidney-specific RNA sequencing and immunohistochemistry data to determine if the mRNA and protein abundance levels are concordant. Our study demonstrates that there is a discordance between mRNA and protein expression in the kidney based on HPA data. Using an external validatory mass spectrometry dataset, we show that more than 500 proteins undetected by immunohistochemistry are robustly measured by mass spectrometry. The HPA transcriptome data, on the other hand, exhibit similar transcript detection levels as other kidney RNA-seq datasets. Such discordance in mRNA-protein expression could be due to both biological and technical reasons, such as transcriptional dynamics, translation rates, protein half-lives, and measurement errors. This is further complicated by the heterogeneity of the kidney tissue itself, which can increase the discordance if the cell populations or tissue compartment samples do not match. As such, shedding light on the mRNA-protein relationship of the kidney-specific HPA data can provide more context to our scientific inferences when we discuss renal gene and protein quantification.
An INS-1 β-cell proteome highlights the role of fatty acid biosynthesis in glucose-stimulated insulin secretion
Authors: Stremmel Nina , Lemke Oliver , Textoris-Taube Kathrin , Ludwig Daniela , Mülleder Michael , Muenzner Julia , Ralser Markus 
Published: July 2024

AbstractPancreatic beta cells secrete insulin as a response to rising glucose level, a process known as glucose-stimulated insulin secretion (GSIS). In this study, we used liquid chromatography tandem mass spectrometry and data-independent acquisition to acquire proteomes of rat pancreatic INS-1 832/13 beta cells that were short-term stimulated with glucose concentrations ranging from 0 to 20 mM, quantifying the behavior of 3703 proteins across 11 concentrations. Ensemble clustering of proteome profiles revealed unique response patterns of proteins expressed by INS-1 cells. 237 proteins, amongst them proteins associated with vesicular SNARE interactions, protein export, and pancreatic secretion showed an increase in abundance upon glucose stimulation, whilst the majority of proteins, including those associated with metabolic pathways such as glycolysis, the TCA cycle and the respiratory chain, did not respond to rising glucose concentrations. Interestingly, we observe that enzymes participating in fatty acid metabolism, responded distinctly, showing a “switch-on” response upon release of glucose starvation with no further changes in abundance upon increasing glucose levels. We speculate that increased activity of fatty acid metabolic activity might either be part of GSIS by replenishing membrane lipids required for vesicle-mediated exocytosis and/or by providing an electron sink to compensate for the increase in glucose catabolism.Significance of the StudyWe used high-throughput proteomics to capture comprehensive proteome changes 30 minutes post stimulation in the INS-1 832/13 beta cell line. Our study provides insights into the metabolic regulation of glucose-stimulated insulin secretion in pancreatic beta cells, specifically highlighting the early role of fatty acid biosynthesis. These findings suggest a necessary shift in focus from electrochemical to metabolic mechanisms in understanding GSIS, paving the way for future research. As the first to document proteome alterations in the initial phase of GSIS, our study furthermore documents the extent of protein abundance variability when obtaining data after short stimulation times, and therefore highlights the necessity of well-controlled study design and biological replicates. The recorded data set complements existing metabolomic and transcriptomic studies, providing a valuable resource for subsequent investigations.
Synchronous theta networks characterize successful memory retrieval
Authors: Rao Aditya M. , DeHaan Riley D. , Kahana Michael J. 
Published: July 2024

AbstractMemory retrieval activates regions across the brain, including not only the hippocampus and medial temporal lobe (MTL), but also frontal, parietal, and lateral temporal cortical regions. What remains unclear, however, is how these regions communicate to organize retrieval-specific process-ing. Here, we elucidate the role of theta (3–8 Hz) synchronization, broadly implicated in memory function, during the spontaneous retrieval of episodic memories. Analyzing a dataset of 382 neurosurgical patients (213 male, 168 female, 1 unknown) implanted with intracranial electrodes who completed a free recall task, we find that synchronous networks of theta phase synchrony span the brain in the moments before spontaneous recall, in comparison to periods of deliberation and incorrect recalls. Hubs of the retrieval network, which systematically synchronize with other regions, appear throughout the prefrontal cortex and lateral and medial temporal lobes, as well as other areas. Theta synchrony increases appear more prominently for slow (3 Hz) theta than for fast (8 Hz) theta in the recall–deliberation contrast, but not in the encoding or recall–intrusion contrast, and theta power and synchrony positively correlate throughout the theta band. These results implicate diffuse brain-wide synchronization of theta rhythms, especially slow theta, in episodic memory retrieval.Significance StatementAnalyzing intracranial recordings from 382 subjects who completed an episodic free recall experi-ment, we study the brain-wide theta synchrony effects of memory retrieval. The literature has not previously described the whole-brain regional distribution of these effects nor studied them with respect to intrusions. We show that a whole-brain theta synchrony effect marks the recall accuracy contrast, that distributed synchronous hubs constitute a whole-brain retrieval network, and that theta synchrony in the successful encoding, successful retrieval, and recall accuracy contrasts corre-lates positively with theta power increases at a region. These findings advance our understanding of the role and localization of theta synchrony effects during human memory retrieval.