bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gustatory-neuron-supplied R-spondin-2 is required for taste bud replenishment
Authors: Xu Jiang , de Araujo Alan Moreira , Xi Ranhui , Lin Xiaoli , Lu Chanyi , Zhou Minliang , Hankenson Kurt , Margolskee Robert F. , Matsumoto Ichiro , de Lartigue Guillaume , Choi Myunghwan , Jiang Peihua 
Published: February 2024

ABSTRACTTaste buds undergo continuous cell turnover throughout life, and taste cell replenishment relies strictly on innervation, a phenomenon first described almost 150 years ago. Recently, we provided evidence that R-spondin 2 (Rspo2) may be the long-sought gustatory neuron-supplied factor that regulates taste stem cell activity, via its interaction with taste stem/progenitor cell-expressed receptor Rnf43/Znrf3. Yet, whether gustatory-neuron-supplied Rspo2 is strictly required for taste tissue maintenance has not been resolved. Here, we set out to determine the necessity of gustatory-neuron-supplied Rspo2 in taste tissue homeostasis using genetic approaches. We used a mouse line that harbors the neomycin-resistance gene (NeoR) in one of the intron regions of theRspo2gene, which results in reduced expression of Rspo2. The number of taste buds is significantly reduced in these mice, compared to wild-type mice, in both anterior and posterior tongue. This phenotypic change was completely reversed by removingNeoRfrom theRspo2gene, thus making it normal. We also combined adeno-associated virus (AAV)-based delivery of Cre recombinase with a mouse line amenable to Cre-based ablation of theRspo2exons encoding the receptor-binding domains. Such deletion of Rspo2 in the nodose-petrosal-jugular ganglion complex led to nearly complete loss of taste buds in the circumvallate papilla. Thus, we demonstrate that Rspo2 is the long-sought gustatory-neuron-supplied factor that acts on taste stem cells to maintain taste tissue homeostasis.SignificanceWe have known for 150 years that innervation is required to induce and maintain cell replacement in taste buds. Until recently, the identity of the inducing factor produced by neurons was unknown. We have shown that R-spondin alone is sufficient to substitute for neuronal input to induce taste bud regeneration. Using a genetic loss-of-function approach, we now demonstrate that gustatory-neuron-expressed Rspo2 is required to maintain taste tissue homeostasis. Altogether, our work reveals that Rspo2 is the long-sought neuron-supplied factor that regulates the activity of taste stem/progenitor cells.
CNVeil enables accurate and robust tumor subclone identification and copy number estimation from single-cell DNA sequencing data
Authors: Yuan Weiman , Luo Can , Hu Yunfei , Zhang Liting , Wen Zihang , Liu Yichen Henrry , Mallory Xian , Zhou Xin Maizie 
Published: February 2024

AbstractSingle-cell DNA sequencing (scDNA-seq) has significantly advanced cancer research by enabling precise detection of chromosomal aberrations, such as copy number variations (CNVs), at a single-cell level. These variations are crucial for understanding tumor progression and heterogeneity among tumor subclones. However, accurate CNV inference in scDNA-seq has been constrained by several factors, including low coverage, sequencing errors, and data variability. To address these challenges, we introduce CNVeil, a robust quantitative algorithm designed to accurately reveal CNV profiles while overcoming the inherent noise and bias in scDNA-seq data. CNVeil incorporates a unique bias correction method using normal cell profiles identified by a PCA-based Gini coefficient, effectively mitigating sequencing bias. Subsequently, a multi-level hierarchical clustering, based on selected highly variable bins, is employed to initially identify coarse subclones for robust ploidy estimation and further identify fine subclones for segmentation. To infer the CNV segmentation landscape, a novel change rate-based across-cell breakpoint identification approach is specifically designed to diminish the effects of low coverage and data variability on a per-cell basis. Finally, a consensus segmentation is utilized to further standardize read depth for the inference of the final CNV profile. In comprehensive benchmarking experiments, where we compared CNVeil with seven state-of-the-art CNV detection tools, CNVeil exhibited exceptional performance across a diverse set of simulated and real scDNA-seq data in cancer genomics. CNVeil excelled in subclone identification, segmentation, and CNV profiling. In light of these results, we anticipate that CNVeil will significantly contribute to single-cell CNV analysis, offering enhanced insights into chromosomal aberrations and genomic complexity.
Ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans
Authors: David Eric T. , Yousuf Muhammad Saad , Mei Hao-Ruei , Jain Ashita , Krishnagiri Sharada , Srikanth Kolluru D. , Dussor Gregory , Dalva Matthew B. , Price Theodore J. 
Published: February 2024

AbstractEphrin-B-EphB signaling promotes pain through signaling between dorsal root ganglion (DRG) neurons and spinal cord neurons in the dorsal horn, and through signaling between peripheral cells and EphB receptors expressed by DRG neurons. Previous findings link ephrin-B expression in painful peripheral tissues in patients to chronic pain, suggesting the clinical significance of this signaling, but the direct effects of ephrins on DRG neurons have not been widely studied. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Our work demonstrates that ephrin-B2-EphB2 signaling drives activation of MNK-eIF4E in DRG neurons to cause an enhanced response to inflammatory mediator signaling in both mice and humans and hyperalgesic priming in two models in mice. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE2injection into the same hindpaw. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1knockout mice) and by the MNK inhibitor eFT508. Similar effects on hyperalgesic priming were seen in a dural injection model. We generated a sensory neuron specific knockout of EphB2 using Pirt-Cre mice and found that these mice lacked responses to ephrin-B2 injection. We used Ca2+-imaging to determine direct effects of ephrin-B2 on DRG neurons and found that ephrin-B2 treatment enhanced Ca2+transients in response to PGE2which were absent in DRG neurons from MNK1−/−and EphB2-PirtCremice. In experiments on human DRG neurons we found that ephrin-B2 increased eIF4E phosphorylation and enhanced Ca2+responses to PGE2treatment, both of which were blocked by eFT508 treatment. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling. The findings offer insight into how ephrin-B signaling promotes pain, and suggests treatment avenues for prevention or reversal of chronic pain associated with EphB activation in sensory neurons.Graphical Abstract
FSTL1 is an antagonist of ERK1/2 phosphorylation during ciliogenesis and preadipocyte differentiation
Authors: Santos Leonardo , Guggeri Lucia , Escande Carlos , Badano José Luis , Prieto-Echagüe Victoria 
Published: February 2024

AbstractFSTL1 is a secreted glycoprotein that is involved in several processes in health and disease, including development, cardiovascular disease, cancer, inflammation, and obesity. The signaling pathways used by FSTL1 to act on target tissues seem to activate different intracellular mediators specific to each tissue and several of the mechanisms of action remain to be determined at the molecular level, including intracellular mediators and receptors. We have previously unveiled a novel role for FSTL1 in ciliogenesis and provided evidence for an Fstl1/cilia axis in preadipocyte differentiation. This pathway is relevant to the pathogenesis of obesity and of a group of conditions called ciliopathies since they are caused by the dysfunction of the primary cilia. This work aimed to identify intracellular mediators of FSTL1 action on ciliogenesis and adipogenesis. We analyzed ERK phosphorylation levels as well as cilia length in the absence of FSTL1 and in the presence of the pERK inhibitor U0126. We also analyzed the differentiation and cilia dynamics of U0126-treated preadipocytes and tested the ERK-mediated signaling by BMP4 in the presence of added extracellular Fstl1. Here, we propose that MAP kinase ERK is a mediator of ciliogenesis downstream of FSTL1 and provide additional data that suggest that FSTL1 antagonizes BMP non-canonical signaling to modulate ciliogenesis and adipogenesis. In sum, our data reinforce the interest on the axis FSTL1/cilia in the modulation of adipogenesis and provide evidence to add ERK to this working model.
Several common methods of making vesicles (except an emulsion method) capture intended lipid ratios
Authors: Weakly Heidi M.J. , Wilson Kent J. , Goetz Gunnar J. , Pruitt Emily L. , Li Amy , Xu Libin , Keller Sarah L. 
Published: February 2024

ABSTRACTResearchers choose different methods of making giant unilamellar vesicles in order to satisfy different constraints of their experimental designs. A challenge of using a variety of methods is that each may produce vesicles of different lipid compositions, even if all vesicles are made from a common stock mixture. Here, we use mass spectrometry to investigate ratios of lipids in vesicles made by five common methods: electroformation on indium tin oxide slides, electroformation on platinum wires, gentle hydration, emulsion transfer, and extrusion. We made vesicles from either 5-component or binary mixtures of lipids chosen to span a wide range of physical properties: di(18:1)PC, di(16:0)PC, di(18:1)PG, di(12:0)PE, and cholesterol. For a mixture of all five of these lipids, ITO electroformation, Pt electroformation, gentle hydration, and extrusion methods result in only minor shifts (≤ 5 mol%) in lipid ratios of vesicles relative to a common stock solution. In contrast, emulsion transfer results in ∼80% less cholesterol than expected from the stock solution, which is counterbalanced by a surprising overabundance of saturated PC-lipid relative to all other phospholipids. Experiments using binary mixtures of some of the lipids largely support results from the 5-component mixture. Exact values of lipid ratios variations likely depend on the details of each method, so a broader conclusion is that experiments that increment lipid ratios in small steps will be highly sensitive to the method of lipid formation and to sample-to-sample variations, which are low (roughly ±2 mol% in the 5-component mixture and either scale proportionally with increasing mole fraction or remain low). Experiments that increment lipid ratios in larger steps or that seek to explain general trends or new phenomena will be less sensitive to the method used.SIGNIFICANCE STATEMENTSmall changes to the amounts and types of lipids in membranes can drastically affect the membrane’s behavior. Unfortunately, it is unknown whether (or to what extent) different methods of making vesicles alter the ratios of lipids in membranes, even when identical stock solutions are used. This presents challenges for researchers when comparing data with colleagues who use different methods. Here, we measure ratios of lipid types in vesicle membranes produced by five methods. We assess each method’s reproducibility and compare resulting vesicle compositions across methods. In doing so, we provide a quantitative basis that the scientific community can use to estimate whether differences between their results can be simply attributed to differences between methods or to sample-to-sample variations.
The influence of environment on mosquito feeding patterns: a meta-analysis of ‘universal’ DNA diet studies in a global context
Authors: O′Rorke Richard , Lee Meshach , Clark Nicholas J. , Webster Tamsyn Uren , Wells Konstans 
Published: February 2024

AbstractMosquitoes have innate preferences for their blood-meal hosts, but these can be modified by the environment, with implications for disease spread under climate and land use change. To predict the spread of vector-borne pathogens more accurately we need to better understand blood-meal plasticity under changing environmental conditions. We compiled blood-meal studies for six prominent disease vectoring mosquitoes from around the globe (Aedes aegypti, Ae. albopictus,Anopheles funestus, An. gambiae,Cx. pipiens, and Cx. quinquefasciatus). We targeted studies that used universal molecular methods (typically PCR/metabarcoding) to identify hosts from a wide range of candidates (as opposed to studies using methods that presuppose host identity - such as precipitin, ELISA). We found that blood-meals from the >15,600 analysed were mostly from the expected host-groups for each mosquito species, but we frequently encountered atypical hosts (e.g. mammalophilic species feeding on birds/reptiles). The universal methods used by the studies in our metanaalysis identified high host richness, and we found ≥174 hosts forCulexand ≤65 species forAedesmosquitoes at a considerably increased discovery rate of novel hosts per sampling effort. We used a hierarchical Dirichlet regression model to analyse global variation in feeding patterns in relation to environmental datasets (land use, precipitation, mean annual temperature, latitude, human and livestock density). Land use, mean annual temperature and poultry density had noticeable effects on blood-meal selection ofAe. aegypti,Cx. pipiensandCx. quinquefasciatus. Although host density was a factor in blood-meal selection - host choice is not a simple function of host availability, as has previously been observed, but contingent on other drivers. While our compiled dataset afforded us these insights, improving resolution and consistency of data gathering and reporting would improve the precision of how blood-meal studies can inform us of present and potential risks of pathogen transmission events.
Cephalopod Sex Determination and its Ancient Evolutionary Origin
Authors: Coffing Gabrielle C. , Tittes Silas , Small Scott T. , Songco-Casey Jeremea O. , Piscopo Denise M. , Pungor Judit R. , Miller Adam C. , Niell Cristopher M. , Kern Andrew D. 
Published: February 2024

SummaryOctopuses, squids, and cuttlefishes – the coleoid cephalopods – are a remarkable branch in the tree of life whose members exhibit a repertoire of sophisticated behaviors (Hanlon and Messenger, 2018). As a clade, coleoids harbor an incredible variety of novel traits including the most complex nervous system among invertebrates, derived camera-type eyes, and rapid adaptive camouflage abilities (Young, 1971; Hanlon, 2007). The burst of evolutionary novelty that distinguishes cephalopods is even more striking in a phylogenetic context; cephalopods are a deeply diverged lineage that last share a common ancestor with other extant molluscs in the Cambrian period, roughly 550 million years ago (Ponder and Lindberg, 2008; Huang et al., 2022). With recent advances in genome sequencing technologies, we have the capability to explore the genomic foundations of cephalopod novelties. Here, using PacBio long-read sequencing of genomic DNA and IsoSeq full-length mRNA sequencing, we provide a novel chromosome-scale reference genome and annotation for a female California two-spot octopus (O. bimaculoides). Our assembly reveals that the female octopus has just one sex chromosome, consistent with a ZO karyotype, while the male has two (ZZ), providing the first evidence of genetic sex determination in cephalopods. We use our assembly and annotation in combination with existing genomic information from other cephalopods to create the first whole genome alignments from this group and demonstrate that the sex chromosome is of an ancient origin, before the radiation of extant cephalopods approximately 480 million years ago (Huang et al., 2022), and has been conserved to the present day in all cephalopod genomes available.
Spherical Echo-Planar Time-resolved Imaging (sEPTI) for rapid 3D quantitative T2* and Susceptibility imaging
Authors: Wang Nan , Liao Congyu , Cao Xiaozhi , Nishimura Mark , Brackenier Yannick WE , Yurt Mahmut , Gao Mengze , Abraham Daniel , Alkan Cagan , Iyer Siddharth Srinivasan , Zhou Zihan , Kerr Adam , Haldar Justin P. , Setsompop Kawin 
Published: February 2024

AbstractPurposeTo develop a 3D spherical EPTI (sEPTI) acquisition and a comprehensive reconstruction pipeline for rapid high-quality whole-brain submillimeter T2* and QSM quantification.MethodsFor the sEPTI acquisition, spherical k-space coverage is utilized with variable echo-spacing and maximum kxramp-sampling to improve efficiency and incoherency when compared to existing EPTI approaches. For reconstruction, an iterative rank-shrinking B0estimation and odd-even high-order phase correction algorithms were incorporated into the reconstruction to better mitigate artifacts from field imperfections. A physics-informed unrolled network was utilized to boost the SNR, where 1-mm and 0.75-mm isotropic whole-brain imaging were performed in 45 and 90 seconds, respectively. These protocols were validated through simulations, phantom, and in vivo experiments. Ten healthy subjects were recruited to provide sufficient data for the unrolled network. The entire pipeline was validated on additional 5 healthy subjects where different EPTI sampling approaches were compared. Two additional pediatric patients with epilepsy were recruited to demonstrate the generalizability of the unrolled reconstruction.ResultssEPTI achieved 1.4 × faster imaging with improved image quality and quantitative map precision compared to existing EPTI approaches. The B0 update and the phase correction provide improved reconstruction performance with lower artifacts. The unrolled network boosted the SNR, achieving high-quality T2* and QSM quantification with single average data. High-quality reconstruction was also obtained in the pediatric patient using this network.ConclusionsEPTI achieved whole-brain distortion-free multi-echo imaging and T2* and QSM quantification at 0.75 mm in 90 seconds which has the potential to be useful for wide clinical applications.
Discovery and Repurposing of Pharmaceutical Agents as Antifungals:In vivoactivity againstCoccidioides
Authors: Mead Heather L. , Valentine Michael , Yin Holly , Thompson George R. , Keim Paul , Engelthaler David M. , Barker Bridget M. 
Published: February 2024

ABSTRACTThere is significant interest in identifying improved treatments for coccidioidomycosis, an endemic fungal infection found in the southwestern United States, and Central and South America. The current standard of care, fluconazole, often fails to completely eradicateCoccidioidesinfection; however, the cost of identifying new compounds is often high in terms of both finances and time. Therefore, repurposing existing pharmaceutical agents is an attractive option. In our previous work, we identified several compounds which inhibited fungal growthin vitro. Based on these findings, we screened a subset of these agents to increase the performance of fluconazole in a combination therapy approach, as compared to fluconazole alone, in a murine model. We observed that combination therapy of sertraline:fluconazole significantly reduced the amount of live fungus in the lung compared to fluconazole alone. These results suggest that sertraline can be repurposed as an adjunctive agent in the treatment of this important fungal disease.
Investigating the effects of repetitive paired-pulse transcranial magnetic stimulation on visuomotor training using TMS-EEG
Authors: Sasaki Ryoki , Hand Brodie J. , Liao Wei-Yeh , Semmler John G. , Opie George M. 
Published: February 2024

AbstractObjectivesI-wave periodicity repetitive paired-pulse transcranial magnetic stimulation (iTMS) can modify acquisition of a novel motor skill, but the associated neurophysiological effects remain unclear. The current study therefore used combined TMS-electroencephalography (TMS-EEG) to investigate the neurophysiological effects of iTMS on subsequent visuomotor training (VT).MethodsSixteen young adults (26.1 ± 5.1 years) participated in three sessions including real iTMS and VT (iTMS + VT), control iTMS and VT (iTMSsham+ VT), or iTMS alone. Motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs) were measured before and after iTMS, and again after VT, to assess neuroplastic changes.ResultsIrrespective of the intervention, MEP amplitude was not changed after iTMS or VT (P= 0.211). Motor skill was improved compared with baseline (P< 0.001), but no differences were found between stimulus conditions. In contrast, the P30 peak was altered by VT when preceded by sham iTMS (P< 0.05), but this effect was not apparent when VT was preceded by iTMS or following iTMS alone (allP> 0.15).ConclusionIn contrast to expectations, iTMS was unable to modulate MEP amplitude or influence motor learning. Despite this, changes in P30 amplitude suggested that motor learning was associated with altered cortical reactivity. Furthermore, this effect was abolished by priming with iTMS, suggesting an influence of priming that failed to impact learning.Authorship statementsConceptualization: JGS; Data curation: RS, BJH, and WL; Formal analysis: RS; Funding acquisition: RS; Investigation: RS, BJH, and WL; Methodology: RS, GMO, BJH and JGS; Project administration: GMO and JGS; Supervision: GMO and JGS; Roles/Writing - original draft: RS and GMO; Writing - review & editing: BJH, WL, and JGS.
Convergent evolution of plant prickles is driven by repeated gene co-option over deep time
Authors: Satterlee James W. , Alonso David , Gramazio Pietro , Jenike Katharine M. , He Jia , Arrones Andrea , Villanueva Gloria , Plazas Mariola , Ramakrishnan Srividya , Benoit Matthias , Gentile Iacopo , Hendelman Anat , Shohat Hagai , Fitzgerald Blaine , Robitaille Gina M. , Green Yumi , Swartwood Kerry , Passalacqua Michael J. , Gagnon Edeline , Hilgenhof Rebecca , Huggins Trevis D. , Eizenga Georgia C. , Gur Amit , Rutten Twan , Stein Nils , Yao Shengrui , Bellot Clement , Bendahmane Mohammed , Frary Amy , Knapp Sandra , Särkinen Tiina , Gillis Jesse , Van Eck Joyce , Schatz Michael C. , Eshed Yuval , Prohens Jaime , Vilanova Santiago , Lippman Zachary B. 
Published: February 2024

AbstractAn enduring question in evolutionary biology concerns the degree to which episodes of convergent trait evolution depend on the same genetic programs, particularly over long timescales. Here we genetically dissected repeated origins and losses of prickles, sharp epidermal projections, that convergently evolved in numerous plant lineages. Mutations in a cytokinin hormone biosynthetic gene caused at least 16 independent losses of prickles in eggplants and wild relatives in the genusSolanum. Strikingly, homologs promote prickle formation across angiosperms that collectively diverged over 150 million years ago. By developing newSolanumgenetic systems, we leveraged this discovery to eliminate prickles in a wild species and an indigenously foraged berry. Our findings implicate a shared hormone-activation genetic program underlying evolutionarily widespread and recurrent instances of plant morphological innovation.