bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lgr5+ductal cells of von Ebner’s glands are stem cells for turnover of posterior tongue taste buds
Authors: Harrison Theresa A. , Downs Anthony M. , Slepian Alexandria J. , van Es Johan H. , Clevers Hans , Defoe Dennis M. 
Published: April 2024

AbstractTaste bud cells have a limited lifespan and must be continuously replaced along with the papilla epithelium in which they reside. Previous work has shown that expression of leucine- rich G protein-coupled receptor 5 (Lgr5), a Wnt pathway agonist, serves as a marker of adult stem/progenitor cells for taste buds located in posterior tongue (circumvallate and foliate), but not anterior tongue (fungiform), taste papillae. However, the specific location/niche of theLgr5-expressing cells supporting renewal and their phenotypic properties have not been fully explored. To address this, the genesis and fate of Lgr5+cells were examined in developing and adult mice using genetic reporter strains. Evidence fromLgr5-lacZandLgr5-GFPmice shows that, whileLgr5is broadly expressed in the epithelium of nascent circumvallate papillae and their trenches during embryonic development, it becomes concentrated within the ducts of adjacent von Ebner’s salivary glands during the first postnatal week, co-incident with the appearance of differentiated taste buds. In posterior tongue taste papillae of adult animals, sites of highestLgr5expression are found in excretory ducts, restricted to the outer (basal) layer of the bi-layered excretory zone. These Lgr5+cells are immunoreactive for keratin 14, like cells in the basal layer of extragemmal taste epithelium, and for Sox9, a marker of exocrine gland duct cells. Lineage tracing experiments with anLgr5-EGFP-IRES-CreERT2;R26-mTmGreporter show that Lgr5+ductal cells become labeled one day following Cre induction, prior to the appearance of descendent cells in taste buds and extragemmal epithelium. These data support a role for Lgr5+ductal cells as stem cells and suggest that a cooperative interaction exists between posterior taste epithelium and its associated salivary glands in taste cell turnover.
Enforced MYC expression selectively redirects transcriptional programs during human plasma cell differentiation
Authors: Vardaka Panagiota , Page Eden , Care Matthew A , Stephenson Sophie , Kemp Ben , Umpierrez Michelle , O’Callaghan Eleanor , Mabbutt Adam , Owen Roger , Hodson Daniel J , Doody Gina M , Tooze Reuben M 
Published: April 2024

AbstractMYC provides a rheostat linking cell growth and division during plasma cell (PC) differentiation. Precise control of MYC is central to the network controlling differentiation. Deregulation of MYC drives transformation in aggressive B-cell neoplasms and is often accompanied by apoptotic protection conferred by BCL2. We assess how MYC and BCL2 deregulation impacts on the ability of human B-cells to complete PC differentiation. Under permissive conditions for PC differentiation we find such deregulation does not transform cells. While driving loss of normal PC surface phenotype, MYC deregulation has little impact on components of regulatory circuitry controlling B-cell identity. This contrasts with profound impact on initiation of secretory output and secretory reprogramming, coupled to dampening ofXBP1and immunoglobulin gene enhancement and a shift toward distinct metabolic programs. The establishment of this aberrant state depends on MYC homology boxes (MB0 and MBII). Dependence on MBII is profound and resolves to residue W135.
A scoping review of evidence of naturally occurring Japanese encephalitis infection in vertebrate animals other than humans, ardeid birds and pigs
Authors: Levesque Zoë A. , Walsh Michael , Webb Cameron , Zadoks Ruth , Brookes Victoria J. 
Published: April 2024

ABSTRACTJapanese encephalitis virus (JEV) is the leading cause of human encephalitis in Asia. JEV is a vector-borne disease, mainly transmitted byCulexmosquitoes, withArdeidaebirds as maintenance hosts and pigs as amplifying hosts. Other vertebrate animal hosts have been suggested to play a role in the epidemiology of JEV. This scoping review followed PRISMA guidelines to identify species in which evidence of naturally occurring JEV infection was detected in vertebrates other than ardeid birds, pigs and people. Following systematic searches, 4372 records were screened, and data were extracted from 62 eligible studies. Direct evidence (virus, viral antigen or viral RNA) of JEV infection was identified in a variety of mammals and birds (not always identified to the species level), including bats, passerine birds (family Turdidae), livestock (cattle [Bos taurus] and a goat [Capra hircus]), carnivores (two meerkats [Suricata suricatta]), and one horse (Equus caballus). Bat families included Pteropodidae, Vespertilionidae, Rhinolophidae, Miniopteridae, Hipposideridae. Indirect evidence suggestive of JEV infection (antibodies) was detected in several mammalian and avian orders, as well as reported in two reptile species. However, a major limitation of the evidence of JEV infection identified in this review was diagnostic test accuracy, particularly for serological testing. Studies generally did not report diagnostic sensitivity or specificity. Although we hypothesise that bats and passerine birds could play an underappreciated role in JEV epidemiology, development of diagnostic tests to differentiate JEV from other orthoflaviviruses will be critical for effective surveillance in these, as well as the companion and livestock species that could be used to evaluate JEV control measures in currently endemic regions.
Genetic purging of strongly deleterious mutations underlies black-necked crane’s unusual escape from an extinction vortex
Authors: Cui Ning , Ma Xuntao , Wu Heqi , Chen Xiaocheng , Hung Chih-Ming , Zhang Lixun , Lei Fumin , Yang Le , Yan Dao , Yang Xiaojun , Dong Feng 
Published: April 2024

AbstractMany species are undergoing rapid demographic declines, necessitating an examination of the resulting genetic impacts. The prevailing small population paradigm posits an elevated genetic load and extinction risk. However, instances of fast recovery from severe population bottlenecks suggest alternative outcomes. To investigate this issue, we performed a population genomic analysis on the black-necked crane, analyzing 42 modern and 11 historical genomes. This study revealed substantial evidence of large-effect allele purging underlying the unexpectedly rapid population recovery following an abrupt bottleneck during the 1980s. Nevertheless, forward simulations supposing a prolonged bottleneck (e.g., five generations) predicted a reversion with negative prospects, implying that rapid population recovery served as both the cause and consequence of the species escaping from an extinction vortex. These findings shed light on a potential positive microevolutionary response to current widespread population collapses and underscore the urgency of implementing active and effective conservation strategies to reverse this trend before it becomes irreversible.
Dynamic modelling of signalling pathways when ODEs are not feasible
Authors: Rachel Timo , Brombacher Eva , Wöhrle Svenja , Groß Olaf , Kreutz Clemens 
Published: April 2024

AbstractMotivationMathematical modelling plays a crucial role in understanding inter- and intracellular signalling processes. Currently, ordinary differential equations (ODEs) are the predominant approach in systems biology for modelling such pathways. While ODE models offer mechanistic interpretability, they also suffer from limitations, including the need to consider all relevant compounds, resulting in large models difficult to handle numerically and requiring extensive data.ResultsIn previous work, we introduced theretarded transient function (RTF)as an alternative method for modelling temporal responses of signalling pathways. Here, we extend the RTF approach to integrate concentration or dose-dependencies into the modelling of dynamics. With this advancement, RTF modelling now fully encompasses the application range of ordinary differential equation (ODE) models, which comprises predictions in both time and concentration domains. Moreover, characterizing dose-dependencies provides an intuitive way to investigate and characterize signalling differences between biological conditions or cell-types based on their response to stimulating inputs. To demonstrate the applicability of our extended approach, we employ data from time- and dose-dependent inflammasome activation in bone-marrow derived macrophages (BMDMs) treated with nigericin sodium salt. Our results show the effectiveness of the extended RTF approach as a generic framework for modelling dose-dependent kinetics in cellular signalling. The approach results in intuitively interpretable parameters that describe signal dynamics and enables predictive modelling of time- and dose-dependencies even if only individual cellular components are quantified.AvailabilityThe presented approach is available within the MATLAB-basedData2Dynamicsmodelling toolbox athttps://github.com/Data2Dynamicsandhttps://zenodo.org/records/14008247and as R code athttps://github.com/kreutz-lab/RTF.Contactclemens.kreutz@uniklinik-freiburg.de
Multiple endocrine defects in adult-onset Sprouty1/2/4 triple knockout mice
Authors: Altés Gisela , Olomí Anna , Perramon-Güell Aida , Hernández Sara , Casanovas Anna , Pérez Aurora , Díaz-Tocados Juan Miguel , Valdivielso José Manuel , Megino Cristina , Navaridas Raúl , Matias-Guiu Xavier , Klein Ophir D. , Egea Joaquim , Dolcet Xavi , Yeramian Andrée , Encinas Mario 
Published: April 2024

ABSTRACTGenes of the Sprouty family (Spry1-4) are feedback inhibitors of receptor tyrosine kinases, especially of Ret and the FGF receptors. As such, they play distinct and overlapping roles in embryo morphogenesis and are considered to be tumor suppressors in adult life. Genetic experiments in mice have defined in great detail the role of these genes during embryonic development, however their function in adult mice is less clearly established. Here we generate adult-onset, whole body Spry1/2/4 triple knockout mice. Tumor incidence in triple mutant mice is comparable to that of wild type littermates of up to one year of age, indicating that Sprouty loss per se is not sufficient to initiate tumorigenesis. On the other hand, triple knockout mice do not gain weight as they age, show less visceral fat, and have lower plasma glucose levels than wild type littermates, despite showing similar food intake and slightly reduced motor function. They also show alopecia, eyelid inflammation, and mild hyperthyroidism. Finally, triple knockout mice present phosphaturia and hypophosphatemia, suggesting exacerbated signaling downstream of FGF23. In conclusion, triple knockout mice develop a series of endocrine abnormalities but do not show increased tumor incidence.
Myosin II actively regulatesDrosophilaproprioceptors
Authors: Guan Chonglin , Nishi Kengo , Kreis Christian T. , Bäumchen Oliver , Göpfert Martin C. , Schmidt Christoph F. 
Published: April 2024

AbstractAuditory receptors can be motile to actively amplify their mechanical input. Here we describe a novel and different type of motility that, residing in supporting cells, shapes physiological responses of mechanoreceptor cells. InDrosophilalarvae, supporting cap cells transmit mechanical stimuli to proprioceptive chordotonal neurons. We found that the cap cells are strongly pre-stretched at rest to twice their relaxed length. The tension in these cells is modulated by non-muscle myosin-II motors. Activating the motors optogenetically causes contractions of the cap cells. Cap-cell-specific knockdown of the regulatory light chain of myosin-II alters mechanically evoked receptor neuron responses, converting them from phasic to more tonic, impairing sensory adaptation. Hence, two motile mechanisms seem to operate in concert in insect chordotonal organs, one in the sensory receptor neurons, based on dynein, and the other in supporting cells, based on myosin.One Sentence SummaryMyosin II motors in contractile cells pre-stretchDrosophilastretch receptors.
Suppression of bacterial cell death underlies the antagonistic interaction between ciprofloxacin and tetracycline inEscherichia coli
Authors: Broughton James , Fraisse Achille , Karoui Meriem El 
Published: April 2024

AbstractAntibiotic combinations are an attractive strategy to maximise the efficiency of drug treatment and minimise resistance evolution, but we still lack a full understanding of their effect on bacterial cells. The interaction between DNA-targeting antibiotics, such as ciprofloxacin, and translation inhibitors, such as tetracycline, is antagonistic, resulting in a weaker effect on bacterial growth than expected from the effect of each single drug. This antagonism has been analysed in detail at the population level, but we lack a single-cell understanding of its effect and how it depends on nutrient availability. Here, we used a microfluidic device to quantify the antagonism between ciprofloxacin and tetracycline at the single-cell level in three nutrient conditions. We showed that improved growth is due to increased survival of cells under the drug combination compared to ciprofloxacin alone. This effect is growth-dependent, with better suppression in rich nutrient conditions. Quantification of the DNA damage response (SOS response) revealed two sub-populations among the cells that die upon ciprofloxacin treatment, with some cells reaching a very high level of SOS while others had a lower level of SOS, similar to surviving cells. The low-SOS cells were more frequent in fast growth conditions and showed increased survival under the drug combination but the high-SOS cells were hardly rescued by the drug combination. This result explains the stronger antagonistic effect of tetracycline on ciprofloxacin in fast growth compared to slow growth. Our results underscore the importance of single-cell quantification in understanding the bacterial response to antibiotic combinations and devising new treatment strategies.
Multi-omic Analysis Identifies Glioblastoma Dependency on H3K9me3 Methyltransferase Activity
Authors: Xie Qiqi , Du Yuanning , Ghosh Sugata , Rajendran Saranya , Cohen-Gadol Aaron A. , Baizabal José-Manuel , Nephew Kenneth P. , Han Leng , Shen Jia 
Published: April 2024

AbstractHistone H3 Lysine 9 dimethylation or trimethylation (H3K9me2 or H3K9me3) marks more than half of the human genome, particularly in heterochromatin regions and specific genes within euchromatic regions. Enzymes catalyzing the methylation of H3K9 have individually been associated with the modulation of gene expression patterns involved in cancer progression, including suppressor of variegation 3-9 homologue 1 (SUV39H1), SUV39H2, SET domain bifurcated 1 (SETDB1), SETDB2, euchromatic histone-lysine N-methyltransferase 1 and 2 (EHMT1/2). However, a comprehensive comparison and understanding of the characteristics and mechanisms of these chromatin-modifying enzymes in cancers remains incompletely understood. In this study, we demonstrated that these six H3K9 methyltransferases differentially expressed in tumors and correlated expression with somatic copy number variations (CNVs) and DNA methylation patterns. Through integrative multi-omics analyses, we identified SUV39H1, SUV39H2, and SETDB1 as the key players among the six H3K9 methyltransferases that exhibited the most significant associations with cancer phenotypes. By incorporating SUV39H1, SUV39H2, and SETDB1, we developed a novel signature termed “H3K9me3 MtSig” (H3K9me3 methyltransferases signature). H3K9me3 MtSig was unique for various tumor types, had prognostic implications and was linked to significant signaling pathways, particularly in glioblastoma (GBM). Furthermore, elevated H3K9me3 MtSig was confirmed in GBM patient-derived cells and tissues. In addition, single-cell expression analysis of H3K9me3 MtSig in GBM tissues demonstrated a pattern related to the G2/M cell cycle and was negatively correlated with immune responses. H3K9me3-mediated repetitive sequence silencing by H3K9me3 MtSig, determined using ChIP-sequencing, contributed to these phenotypes, and inhibiting H3K9me3 MtSig in patient-derived GBM cells suppressed proliferation and increased immune responses. Translationally, H3K9me3 MtSig performed as an independent prognostic factor in a clinical prediction model, and drug susceptibility screening integrating H3K9me3 MtSig identified potential biomarkers and therapeutics for GBM. In summary, H3K9me3 MtSig has the potential to elucidate novel prognostic markers, therapeutic targets, and predictors of treatment response in GBM and other cancer types for clinical intervention.SignificanceDifferential expressions of H3K9 methyltransferases across cancers correlates with clinical outcomes; in GBM, an H3K9me3 methyltransferase signature links to G2/M cell cycle, immune response pathways, and prognosis, aiding biomarker and treatment development.
Elevated DNA Damage without signs of aging in the short-sleeping Mexican Cavefish
Authors: Lloyd Evan , Xia Fanning , Moore Kinsley , Zertuche Carolina , Rastogi Aakriti , Kozol Rob , Kenzior Olga , Warren Wesley , Appelbaum Lior , Moran Rachel L. , Zhao Chongbei , Duboue Erik , Rohner Nicolas , Keene Alex C. 
Published: April 2024

AbstractDysregulation of sleep has widespread health consequences and represents an enormous health burden. Short-sleeping individuals are predisposed to the effects of neurodegeneration, suggesting a critical role for sleep in the maintenance of neuronal health. While the effects of sleep on cellular function are not completely understood, growing evidence has identified an association between sleep loss and DNA damage, raising the possibility that sleep facilitates efficient DNA repair. The Mexican tetra fish,Astyanax mexicanusprovides a model to investigate the evolutionary basis for changes in sleep and the consequences of sleep loss. Multiple cave-adapted populations of these fish have evolved to sleep for substantially less time compared to surface populations of the same species without identifiable impacts on healthspan or longevity. To investigate whether the evolved sleep loss is associated with DNA damage and cellular stress, we compared the DNA Damage Response (DDR) and oxidative stress levels betweenA. mexicanuspopulations. We measured markers of chronic sleep loss and discovered elevated levels of the DNA damage marker γH2AX in the brain, and increased oxidative stress in the gut of cavefish, consistent with chronic sleep deprivation. Notably, we found that acute UV-induced DNA damage elicited an increase in sleep in surface fish but not in cavefish. On a transcriptional level, only the surface fish activated the photoreactivation repair pathway following UV damage. These findings suggest a reduction of the DDR in cavefish compared to surface fish that coincides with elevated DNA damage in cavefish. To examine DDR pathways at a cellular level, we created an embryonic fibroblast cell line from the two populations ofA. mexicanus. We observed that both the DDR and DNA repair were diminished in the cavefish cells, corroborating thein vivofindings and suggesting that the acute response to DNA damage is lost in cavefish. To investigate the long-term impact of these changes, we compared the transcriptome in the brain and gut of aged surface fish and cavefish. Strikingly, many genes that are differentially expressed between young and old surface fish do not transcriptionally vary by age in cavefish. Taken together, these findings suggest that cavefish have developed resilience to sleep loss, despite possessing cellular hallmarks of chronic sleep deprivation.
Dependence of Contextual Modulation in Macaque V1 on Interlaminar Signal Flow
Authors: Zhu Shude , Oh Yu Jin , Trepka Ethan B. , Chen Xiaomo , Moore Tirin 
Published: April 2024

AbstractIn visual cortex, neural correlates of subjective perception can be generated by modulation of activity from beyond the classical receptive field (CRF). In macaque V1, activity generated by nonclassical receptive field (nCRF) stimulation involves different intracortical circuitry than activity generated by CRF stimulation, suggesting that interactions between neurons across V1 layers differ under CRF and nCRF stimulus conditions. Using Neuropixels probes, we measured border ownership modulation within large, local populations of V1 neurons. We found that neurons in single columns preferred the same side of objects located outside of the CRF. In addition, we found that cross-correlations between pairs of neurons situated across feedback/horizontal and input layers differed between CRF and nCRF stimulation. Furthermore, independent of the comparison with CRF stimulation, we observed that the magnitude of border ownership modulation increased with the proportion of information flow from feedback/horizontal layers to input layers. These results demonstrate that the flow of signals between layers covaries with the degree to which neurons integrate information from beyond the CRF.
hyve, a compositional visualisation engine for brain imaging data
Authors: Ciric Rastko , Xu Anna , Poldrack Russell A. 
Published: April 2024

AbstractVisualisations facilitate the interpretation of geometrically structured data and results. However, heterogeneous geometries—such as volumes, surfaces, and networks—have traditionally mandated different software approaches. We introducehyve, a Python library that uses a compositional functional framework to enable parametric implementation of custom visualisations for different brain geometries. Under this framework, users compose a reusable visualisation protocol fromgeometricprimitives for representing data geometries,inputprimitives for common data formats and research objectives, andoutputprimitives for producing interactive displays or configurable snapshots.hyvealso writes documentation for user-constructed protocols, automates serial production of multiple visualisations, and includes an API for semantically organising an editable multi-panel figure. Through the seamless composition of input, output, and geometric primitives,hyvesupports creating visualisations for a range of neuroimaging research objectives.