bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of taste processing shifts dietary preference
Authors: Bertolini Enrico , Münch Daniel , Pascual Justine , Sgammeglia Noemi , Ribeiro Carlos , Auer Thomas O. 
Published: October 2024

AbstractFood choice is an important driver of speciation and invasion of novel ecological niches. However, we know little about the mechanisms leading to changes in dietary preference. Here, we use the three closely-related speciesDrosophila sechellia,D. simulansandD. melanogasterto study taste circuit and food choice evolution.D. sechellia,a host specialist, feeds exclusively on a single fruit (Morinda citrifolia, noni) - the latter two are generalists living on various substrates. Using quantitative feeding assays, we recapitulate the preference for noni inD. sechelliaand detect conserved sweet but altered bitter sensitivity via calcium imaging in peripheral taste neurons. Noni surprisingly activates bitter sensing neurons more strongly inD. sechelliadue to a small deletion in one single gustatory receptor. Using volumetric calcium imaging in the ventral brain, we show that instead of peripheral physiology, species-specific processing of noni and sugar signals in sensorimotor circuits recapitulates differences in dietary preference. Our data support that peripheral receptor changes alone cannot explain altered food choice but rather modifications in how sensory information is transformed into feeding motor commands.
The consonance of chords: The effect of subsemitone changes to each of the notes in a trichord on its perceived consonance
Authors: Varkevisser J.M. , Kruitwagen J.M. , Spierings M. J. 
Published: October 2024

AbstractConsonance plays a key role in how listeners experience music, but the factors influencing consonance perception remain a topic of discussion, for instance regarding the role of the familiarity of note combinations. Previous empirical studies of consonance have used common, familiar chords, making it harder to separate the effect of acoustic features from familiarity. Here we explored consonance perception in an unfamiliar, non-standardly tuned 0-5-10 trichord. A test was conducted in which 100 musicians and 100 nonmusicians compared the consonance of an original, non-standard, 0-5-10 chord and an adapted version, in which the lowest, middle or upper note was raised or lowered with 25 or 50 cents. According to a model based on continuous acoustic features, any adaptation to a 0-5-10 chord should yield a comparable decrease in consonance. We indeed found a general consonance decrease, but this was stronger for adaptations enlarging the distance between the lowest and the upper note, i.e. lowering the lowest or raising the highest note, than for other adaptations. These results deviate from the model’s predictions and from patterns observed in standard, more familiar chords. Future research should examine the generalizability of these findings to other chords than the 0-5-10 trichord.
STAT3 signalling enhances tissue expansion during postimplantation mouse development
Authors: Azami Takuya , Theeuwes Bart , Ton Mai-Linh N , Mansfield William , Harland Luke , Kinoshita Masaki , Gottgens Berthold , Nichols Jennifer 
Published: October 2024

AbstractSTAT3 signalling has been studied extensively in the context of self-renewal and differentiation of mouse embryonic stem cells. Zygotic STAT3 is required for normal postimplantation development. On an outbred genetic background,Stat3null embryos consistently lagged behind their littermates, beginning with significant reduction of epiblast cells at implantation. Remarkably, mutants closely resemble non-affected embryos from the previous day at all postimplantation stages examined. We pinpoint this phenotype to loss of the serine-phosphorylated form of STAT3 which predominates in postimplantation embryonic tissues. Bulk RNA-sequencing analysis of isolated mouse epiblasts confirmedStat3null embryos exhibited developmental delay transcriptionally. Single cell RNA sequencing of mid gestation chimaeras containing STAT3 null embryonic stem cells revealed exclusion of mutant cells exclusively from the erythroid lineage. Although Stat3 null embryonic stem cells can differentiate into erythroid and hematopoietic lineages in vitro, they are out-competed when mixed with wild type cells. Combined with the reduced size of STAT3 null epiblasts after implantation, our results implicate a role for STAT3 in cell proliferation affecting temporal control of embryonic progression and rapid differentiation.For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Functional contribution of astrocytic Kir4.1 channels to spasticity after spinal cord injury
Authors: Barbay Tony , Pecchi Emilie , Franco Jose Jorge Ramirez , Ivanov Anton , Brocard Frédéric , Rouach Nathalie , Bos Rémi 
Published: October 2024

SummarySpasticity, a prevalent motor issue characterized by network hyperexcitability, causes pain and discomfort, with existing treatments offering limited relief. While past research has focused on neuronal factors, the role of astrocytes in spasticity has been overlooked. This study explores the potential of restoring astrocytic potassium (K+) uptake to reduce spasticity following SCI. Astrocytes buffer extracellular K+via Kir4.1 channels, preventing neuronal hyperexcitability. Following spinal cord injury (SCI), Kir4.1 levels decrease at the injury site, though the consequences and mechanisms of this reduction within the motor output area have not been investigated. Utilizing advanced techniques, we demonstrate that lumbar astrocytes in a juvenile thoracic SCI mouse model switch to reactive phenotype, displaying morpho-functional and pro-inflammatory changes. These astrocytes also experience NBCe1-mediated intracellular acidosis, leading to Kir4.1 dysfunction and impaired K+uptake. Enhancing Kir4.1 function reduces spasticity in SCI mice, revealing new therapeutic targets for neurological diseases associated with neuronal hyperexcitability.HighlightsLumbar astrocytes adopt a reactive phenotype following a thoracic SCINBCe1-mediated acidosis in astrocytes disrupts Kir4.1 function post-SCI.Impaired K+ uptake leads to motoneuron hyperexcitability post-SCI.Enhanced astroglial Kir4.1 function reduces spastic-like symptoms in SCI mice.
Fetal Liver-like Organoids Recapitulate Blood-Liver Niche Development and Multipotent Hematopoiesis from Human Pluripotent Stem Cells
Authors: Rezvani Milad , Lewis Kyle , Quach Susanna , Iwasawa Kentaro , Weihs Julian , Reza Hasan Al , Cai Yuqi , Kimura Masaki , Zhang RanRan , Milton Yuka , Chaturvedi Praneet , Thorner Konrad , Nayak Ramesh C. , Munera Jorge , Kramer Phillip , Davis Brian R. , Balamurugan Appakalai N. , Ahmed Yeni Ait , Finke Marcel , Behncke Rose Yinghan , Guillot Adrien , Hägerling René , Polansky Julia K. , Bufler Philip , Cancelas Jose A , Wells James M. , Yoshimoto Momoko , Takebe Takanori 
Published: October 2024

SUMMARYThe fetal liver is a hematopoietic organ, hosting a diverse and evolving progenitor population. While human liver organoids derived from pluripotent stem cells (PSCs) mimic aspects of embryonic and fetal development, they typically lack the complex hematopoietic niche and the interaction between hepatic and hematopoietic development. We describe the generation of human Fetal Liver-like Organoids (FLOs), that model human hepato-hematopoietic interactions previously characterized in mouse models. Developing FLOs first integrate a yolk sac-like hemogenic endothelium into hepatic endoderm and mesoderm specification. As the hepatic and hematopoietic lineages differentiate, the FLO culture model establishes an autonomous niche capable of driving subsequent progenitor differentiation without exogenous factors. Consistent with yolk sac-derived waves, hematopoietic progenitor cells (HPCs) within FLOs exhibit multipotency with a preference for myeloid lineage commitment, while retaining fetal B and T cell differentiation potential. We reconstruct in FLOs the embryonic monocyte-to-macrophage and granulocyte immune trajectories within the FLO microenvironment and assess their functional responses in the liver niche.In vivo, FLOs demonstrate a liver engraftment bias of hematopoietic cells, recapitulating a key phenomenon of human hematopoietic ontogeny. Our findings highlight the intrinsic capacity of liver organoids to support hematopoietic development, establishing FLOs as a platform for modeling and manipulating human blood-liver niche interactions during critical stages of development and disease.
Astrocyte regional specialization is shaped by postnatal development
Authors: Schroeder Margaret E. , McCormack Dana M. , Metzner Lukas , Kang Jinyoung , Li Katelyn X. , Yu Eunah , Levandowski Kirsten M. , Zaniewski Heather , Zhang Qiangge , Boyden Edward S. , Krienen Fenna M. , Feng Guoping 
Published: October 2024

AbstractAstrocytes are an abundant class of glial cells with critical roles in neural circuit assembly and function. Though many studies have uncovered significant molecular distinctions between astrocytes from different brain regions, how this regionalization unfolds over development is not fully understood. We used single-nucleus RNA sequencing to characterize the molecular diversity of brain cells across six developmental stages and four brain regions in the mouse and marmoset brain. Our analysis of over 170,000 single astrocyte nuclei revealed striking regional heterogeneity among astrocytes, particularly between telencephalic and diencephalic regions, at all developmental time points surveyed in both species. At the stages sampled, most of the region patterning was private to astrocytes and not shared with neurons or other glial types. Though astrocytes were already regionally patterned in late embryonic stages, this region-specific astrocyte gene expression signature changed dramatically over postnatal development, and its composition suggests that regional astrocytes further specialize postnatally to support their local neuronal circuits. Comparing across species, we found divergence in the expression of astrocytic region- and age-differentially expressed genes and the timing of astrocyte maturation relative to birth between mouse and marmoset, as well as hundreds of species differentially expressed genes. Finally, we used expansion microscopy to show that astrocyte morphology is largely conserved across gray matter regions of prefrontal cortex, striatum, and thalamus in the mouse, despite substantial molecular divergence.
tDCS Cranial Nerve Co-Stimulation: Unveiling Brainstem Pathways Involved in Trigeminal Nerve Direct Current Stimulation in Rats
Authors: Majdi Alireza , Larsen Lars E. , Raedt Robrecht , Laughlin Myles Mc 
Published: October 2024

AbstractThe effects of transcranial direct current stimulation (tDCS) are typically attributed to the polarization of cortical neurons by the weak electric fields it generates in the cortex. However, emerging evidence indicates that certain tDCS effects may be mediated through the co-stimulation of peripheral or cranial nerves, particularly the trigeminal nerve (TN), which projects to critical brainstem nuclei that regulate the release of various neurotransmitters throughout the central nervous system. Despite this, the specific pathways involved remain inadequately characterized.In this study, we examined the effects of acute transcutaneous TN direct current stimulation (TN-DCS) on tonic (i.e. mean spike rate and spike rate over time) and phasic (number of bursts, spike rate per burst, burst duration, and inter-burst interval) activities while simultaneously recording single-neuron activity across three brainstem nuclei in rats: the locus coeruleus (LC), dorsal raphe nucleus (DRN), and median raphe nucleus (MnRN).We found that TN-DCS significantly modulated tonic activity in the LC, with notable interactions between stimulation amplitude, polarity, and time epoch affecting mean spike rates. Similar effects were observed in the DRN regarding tonic activity. Further, phasic activity in the LC was influenced by TN-DCS, with changes in burst number, duration, and inter-burst intervals linked to stimulation parameters. Conversely, MnRN tonic activity following TN-DCS remained unchanged. Importantly, xylocaine administration to block TN abolished the effects on tonic activities in both the LC and DRN.These results suggest that tDCS effects may partially arise from indirect modulation of the TN, leading to altered neuronal activity in DRN and LC. Besides, the differential changes in tonic and phasic LC activities underscore their complementary roles in mediating TN-DCS effects on higher cortical regions. This research bears significant translational implications, providing mechanistic insights that could enhance the efficacy of tDCS applications and deepen our understanding of its neurophysiological effects.
Load activated FGFR and beta1 integrins target distinct chondrocyte mechano-response genes
Authors: Dietmar Helen F. , Weidmann Pia A. , Alberton Paolo , Teichwart Terrilyn , Renkawitz Tobias , Vortkamp Andrea , Aszodi Attila , Richter Wiltrud , Diederichs Solvig 
Published: October 2024

ABSTRACTIn response to mechanical stimuli, chondrocytes adapt their transcriptional activity, thereby shaping the cellular mechano-response; however, it remains unclear whether the activation of cell surface receptors during mechanical loading converge in the activation of the same mechano-response genes, or whether pathway-specific genes can be defined. We aimed to determine whether load-activated FGF/FGFR signalling and β1 integrin jointly activate ERK and control the same or distinct subsets of mechano-regulated genes. To this end, tissue-engineered neocartilage was generated from murine costal chondrocytes or human articular chondrocytes and subjected to dynamic unconfined compression with or without FGFR inhibition. To assess the role of β1 integrins, neocartilage was generated from embryonic β1 integrin-deficient or wild type costal chondrocytes.Load-activated FGFR signalling drove ERK activation in murine chondrocytes, and partially also in human chondrocytes, and mechano-response genes could be classified according to their regulation:Fosl1,Itga5, NgfandTimp1were regulated by load-activated FGFR depending on the developmental stage, whereas β1 integrins controlledInhbaexpression. In human chondrocytes, load-activated FGFR controlled expression ofBMP2,PTGS2andDUSP5,but notFOSB.We show here that the chondrocyte loading response is coordinated by concurrent activation of multiple receptors, and identified for the first time distinct target genes of activated receptors. These insights open up the opportunity to pharmacologically shape the mechano-response of chondrocytes in future studies with promising implications for the management of osteoarthritis and the development of novel therapeutic strategies.
Neutral lipids restrict the mobility of broken DNA molecules during comet assays
Authors: Soulet Caroline , Josa-Castro Jordi , Moriel-Carretero María 
Published: October 2024

AbstractOne widespread technique to assess in relative terms the amount of broken DNA present in the genome of individual cells consists in immobilizing the cell’s nucleus under an agarose pad (called the nucleoid) and subject the whole genome to electrophoresis to force broken DNA molecules out of it. Since the migrating DNA molecules create a tail behind the nucleoid, this technique is named the comet assay. While performing comet assays regularly, we systematically observed circular regions devoid of DNA within the nucleoid region. We characterize here that these correspond to clusters of neutral (apolar) lipids, since they could be labelled with neutral lipid-dying molecules, increased when cells were fed with oleic acid, and were irresponsive to the electrophoretic field. Of relevance, de-lipidation assays eitherin vivo, orin vitro, show that these neutral lipids within the nucleoid limit the ability of broken DNA molecules to migrate into the comet tail. From a technical point of view, we show that de-lipidation permits a wider range for the detection of broken DNA molecules. Biologically, we put forward the notion that neutral lipids in contact with DNA may locally exert regulatory functions within the cell’s nucleus.
Light modulates glucose and lipid homeostasis via the sympathetic nervous system
Authors: Chen Xiangning , Lin Eugene , Haghighatian Mozhan M. , Shepard Logan Wallace , Hattar Samer , Kuruvilla Rejji , Zhao Haiqing 
Published: October 2024

AbstractLight is an important environmental factor for vision, and for diverse physiological and psychological functions. Light can also modulate glucose metabolism. Here, we show that in mice, light is critical for glucose and lipid homeostasis by regulating the sympathetic nervous system, independent of circadian disruption. Light deprivation from birth elicits insulin hypersecretion, glucagon hyposecretion, lower gluconeogenesis, and reduced lipolysis by 6- 8 weeks, in male, but not, female mice. These metabolic defects are consistent with blunted sympathetic activity, and indeed, sympathetic responses to a cold stimulus are significantly attenuated in dark-reared mice. Further, long-term dark rearing leads to body weight gain, insulin resistance, and glucose intolerance. Notably, metabolic dysfunction can be partially alleviated by 5 weeks exposure to a regular light-dark cycle. These studies provide insight into circadian-independent mechanisms by which light directly influences whole-body physiology and inform new approaches for understanding metabolic disorders linked to aberrant environmental light conditions.TeaserLight exerts direct circadian-independent effects on glucose and lipid metabolism.
CellMet: Extracting 3D shape metrics from cells and tissues
Authors: Theis Sophie , Mendieta-Serrano Mario A , Chapa-y-Lazo Bernardo , Chen Juliet , Saunders Timothy E 
Published: October 2024

AbstractDuring development and tissue repair, cells reshape and reconfigure to ensure organs take specific shapes. This process is inherently three-dimensional (3D). Yet, in part due to limitations in imaging and data analysis, cell shape analysis within tissues have been studied as a two-dimensional (2D) approximation,e.g., theDrosophilawing disc. With recent advances in imaging and machine learning, there has been significant progress in our understanding of 3D cell and tissue shapein vivo. However, even after gaining 3D segmentation of cells, it remains challenging to extract cell shape metrics beyond volume and surface area for cells within densely packed tissues. In order to extract 3D shape metrics, we have developed CellMet. This user-friendly tool enables extraction of quantitative shape information from 3D cell and tissue segmentation. It is developed for extracting cell scale information from densely packed tissues, such as cell face properties, cell twist, and cell rearrangements. Our method will improve the analysis of 3D cell shape and the understanding of cell organisation within tissues. Our tool is open source, available athttps://github.com/TimSaundersLab/CellMet.
A polymerase ribozyme that can synthesize both itself and its complementary strand
Authors: Gianni Edoardo , Kwok Samantha L. Y. , Wan Christopher J. K. , Goeij Kevin , Clifton Bryce E. , Attwater James , Holliger Philipp 
Published: October 2024

AbstractThe emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes could constitute such a system, but their large size and structural complexity hinder their self-replication and make their spontaneous emergence improbable. Here we describe QT45: a 45-nucleotide ribozyme, discovered from a random sequence pool, that catalyzes general RNA-templated RNA synthesis using trinucleotide triphosphate substrates. QT45 can synthesize both its complementary strand from a mix of all 64 trinucleotides and a copy of itself using 13 defined trinucleotides and one hexamer as substrates. The discovery of this complex activity in a small ribozyme suggests that polymerase ribozymes may be more abundant in RNA sequence space than anticipated, thereby facilitating the emergence of self-replication.
Transient proliferation by reversible YAP and mitogen-control of the cyclin D1/p27 ratio
Authors: Ferrick Katherine R. , Fan Yilin , Ratnayeke Nalin , Teruel Mary N. , Meyer Tobias 
Published: October 2024

ABSTRACTHippo-YAP signaling orchestrates epithelial tissue repair and is therefore an attractive target in regenerative medicine. Yet it is unresolved how YAP integrates with mitogen signaling and contact inhibition to control the underlying transient proliferative response. Here we show that reduced contact inhibition, increased mitogen signaling, and YAP-TEAD activation converge on increasing the nuclear cyclin D1/p27 protein ratio during G1 phase, towards a threshold ratio that dictates whether individual cells enter or exit the cell cycle. YAP increases this ratio indirectly, in concert with mitogen signaling, by increasing EGFR and other receptors that signal primarily through ERK. After a delay, contact inhibition suppresses YAP activity which gradually downregulates mitogen signaling and the cyclin D1/p27 ratio. Increasing YAP activity by ablating the suppressor Merlin/NF2 reveals a balancing mechanism in which YAP suppression and contact inhibition of proliferation can be recovered but only at higher local cell density. Thus, critical for tissue repair, robust proliferation responses result from the YAP-induced and receptor-mediated prolonged increase in the cyclin D1/p27 ratio, which is only reversed by delayed suppression of receptor signaling after contact inhibition of YAP.
Activation of Group II Metabotropic Glutamate Receptors in the Basolateral Amygdala Inhibits Reward Seeking Triggered by Discriminative Stimuli
Authors: LeCocq Mandy Rita , Mainville-Berthiaume Amélie , Laplante Isabel , Samaha Anne-Noël 
Published: October 2024

AbstractReward-associated cues are essential in guiding reward-seeking behaviours. These cues include conditioned stimuli (CSs) which occur following seeking actions and indicate reward delivery, and discriminative stimuli (DSs) which occur response-independently and signal reward availability. Metabotropic group II glutamate (mGlu2/3) receptors in the basolateral amygdala (BLA) modulate CS-guided reward seeking; however, their role in DS effects is unknown. We first developed a procedure to assess DS and CS effects on reward seeking in the same subjects within the same test session. Female and male rats first self-administered sucrose during sessions where discriminative stimuli signaled periods of sucrose availability (DS+) and unavailability (DS-). During DS+ presentations, active lever presses produced sucrose paired with a CS+. During DS-presentations, active lever presses produced a CS- and no sucrose. Across 14 sessions, rats learned to load up on sucrose during DS+ presentation and inhibit responding during DS-presentation. We then compared the effects of intra-BLA microinfusions of the mGlu2/3receptor agonist LY379268 on cue-evoked sucrose seeking during an extinction test (no sucrose) where the DSs and CSs were presented response-independently. Before test, rats received intra-BLA microinjections of artificial cerebrospinal fluid (aCSF) or LY379268. Under aCSF, only the DS+ and DS+CS+ combined triggered increases in reward-seeking behaviour. The CS+ alone was ineffective. Intra-BLA LY379268 reduced sucrose seeking triggered by the DS+ and DS+CS+ combination. Thus, using a new procedure to test reward seeking induced by DSs and CSs, we show that BLA mGlu2/3receptor activity mediates the conditioned incentive motivational effects of reward predictive DSs.