bluuebunny/crossref_metadata_2025_split huggingface dataset:
The parabrachial to central amygdala circuit is a key mediator of injury-induced pain sensitization
Authors: Torres-Rodriguez Jeitzel M. , Wilson Torri D. , Singh Sudhuman , Chaudhry Sarah , Adke Anisha P. , Becker Jordan J. , Lin Jenny L. , Gonzalez Santiago Martinez , Soler-Cedeño Omar , Carrasquillo Yarimar 
Published: February 2023

AbstractThe spino-ponto-amygdaloid pathway is a major ascending circuit relaying nociceptive information from the spinal cord to the brain. Potentiation of excitatory synaptic transmission in the parabrachial nucleus (PbN) to central amygdala (CeA) pathway has been reported in rodent models of persistent pain. At the behavioral level, the PbN→CeA pathway has been proposed to serve as a general alarm system to potential threats that modulates pain-related escape behaviors, threat memory, aversion, and affective-motivational (but not somatosensory) responses to painful stimuli. Increased sensitivity to previously innocuous somatosensory stimulation is a hallmark of chronic pain. Whether the PbN→CeA circuit contributes to heightened peripheral sensitivity following an injury, however, remains unknown. Here, we demonstrate that activation of CeA-projecting PbN neurons contributes to injury-induced behavioral hypersensitivity but not baseline nociception in male and female mice. Using optogenetic assisted circuit mapping, we confirmed a functional excitatory projection from PbN→CeA that is independent of the genetic or firing identity of CeA cells. We then showed that peripheral noxious stimulation increases the expression of the neuronal activity marker c-Fos in CeA-projecting PbN neurons and chemogenetic inactivation of these cells reduces behavioral hypersensitivity in models of neuropathic and inflammatory pain without affecting baseline nociception. Lastly, we show that chemogenetic activation of CeA-projecting PbN neurons is sufficient to induce bilateral hypersensitivity without injury. Together, our results demonstrate that the PbN→CeA pathway is a key modulator of pain-related behaviors that can amplify responses to somatosensory stimulation in pathological states without affecting nociception under normal physiological conditions.Significance StatementEarly studies identified the spino-ponto-amygdaloid pathway as a major ascending circuit conveying nociceptive inputs from the spinal cord to the brain. The functional significance of this circuit to injury-induced hypersensitivity, however, remains unknown. Here, we addressed this gap in knowledge using viral-mediated anatomical tracers,ex-vivoelectrophysiology and chemogenetic intersectional approaches in rodent models of persistent pain. We found that activation of this pathway contributes to injury-induced hypersensitivity, directly demonstrating a critical function of the PbN→CeA circuit in pain modulation.
Inverse-folding design of yeast telomerase RNA increases activityin vitro
Authors: Lebo Kevin J. , Zappulla David C. 
Published: February 2023

ABSTRACTSaccharomyces cerevisiaetelomerase RNA, TLC1, is an 1157 nt non-coding RNA that functions as both a template for DNA synthesis and a flexible scaffold for telomerase RNP holoenzyme protein subunits. The tractable budding yeast system has provided landmark discoveries about telomere biologyin vivo, but yeast telomerase research has been hampered by the fact that the large TLC1 RNA subunit does not support robust telomerase activityin vitro. In contrast, 155–500 nt miniaturized TLC1 alleles comprising the catalytic core domain and lacking the RNA’s long arms do reconstitute robust activity. We hypothesized that full-length TLC1 is prone to misfoldingin vitro. To create a full-length yeast telomerase RNA predicted to fold into its biological relevant structure, we took an inverse RNA folding approach, changing 59 nucleotides predicted to increase the energetic favorability of folding into the modeled native structure based on thep-numfeature ofMfoldsoftware. The sequence changes lowered the predicted ∆G in this “determined-arm” allele, DA-TLC1, by 61 kcal/mol (–19%) compared to wild type. We tested DA-TLC1 for reconstituted activity and found it to be ∼5-fold more robust than wild-type TLC1, suggesting that the inverse-folding design indeed improved foldingin vitrointo a catalytically active conformation. We also tested if DA-TLC1 functionsin vivoand found that it complements atlc1∆ strain, allowing cells to avoid senescence and maintain telomeres of nearly wild-type length. However, all inverse-designed RNAs that we tested had reduced abundancein vivo. In particular, inverse-designing nearly all of the Ku arm caused a profound reduction in telomerase RNA abundance in the cell and very short telomeres. Overall, these results show that inverse design ofS. cerevisiaetelomerase RNA increases activityin vitro, while reducing abundancein vivo. This study provides a biochemically and biologically tested approach to inverse-design RNAs usingMfoldthat could be useful for controlling RNA structure in basic research and biomedicine.
Exceeding 80% efficiency of single-bead encapsulation in microdroplets through hydrogel coating-assisted close-packed ordering
Authors: Chen Long , Zhao Yi , Li Jie , Xiong Chenwei , Xu Yi , Tang Chengren , Zhang Rong , Zhang Jingwei , Mi Xianqiang , Liu Yifan 
Published: February 2023

AbstractHigh-efficiency encapsulation of single microbeads in microdroplets is essential for droplet-based high-throughput analysis such as single-cell genomics and digital immunoassays. However, the demand has been hindered by the Poisson statistics of beads arbitrarily distributed in the droplet partitions. Although techniques such as inertial ordering have been proven useful to improve bead loading efficiency, a general method that requires no advanced microfluidics and owns compatibility with diverse bead types is still highly desired. In this paper, we present hydrogel coating-assisted close-packed ordering, a simple strategy that improves the bead loading efficiency to over 80%. In the strategy, the raw beads are coated with a thin layer of hydrogel to become slightly compressible and lubricious so that they can be close-packed in a microfluidic device and loaded into droplets in a synchronized manner. We first show that the thin hydrogel coating can be realized conveniently through either jetting microfluidics or vortex emulsification. When loading single 30-μm polystyrene beads, we experimentally determined an overall efficiency of 81% with the proposed hydrogel coating strategy. Of note, the strategy is not sensitive to the selection of raw beads and can tolerate their polydispersity. Using the strategy, we achieve a cell capture rate of 68.8% when co-encapsulating HEK293T cells and polydispersed barcoded beads for single-cell transcriptomics. Further sequencing results verify that the reversible hydrogel coating does not affect the RNA capture behavior of the encapsulated barcoded beads. Given its convenience and broad compatibility, we anticipate that our strategy can be applied to various droplet-based high-throughput assays to drastically improve their efficiency.
Extending species-area relationships into the realm of ecoacoustics: The soundscape-area relationship
Authors: Luypaert Thomas , Bueno Anderson S. , Haugaasen Torbjørn , Peres Carlos A. 
Published: February 2023

AbstractThe rise in species richness with area is one of the best-studied patterns in ecology. Yet, little is known about the spatial scaling of alternate dimensions of diversity. Here, we provide empirical evidence for a relationship between the richness of acoustic traits emanating from the landscape, or soundscape richness, and the island area, which we term the Soundscape Area Relationship (SSAR). We show a positive relationship between the gamma soundscape richness and island area, with slope and R2-values of comparable magnitude to those reported in the literature. This relationship breaks down at the smallest spatial scales, indicating a small-island effect. Moreover, we demonstrate a positive spatial scaling of the plot-scale alpha soundscape richness, but not the beta soundscape turnover, suggesting disproportionate effects are an important underlying mechanism. We conclude that the scaling of biodiversity can be extended to the realm of ecoacoustics, implying soundscape metrics are sensitive to fundamental ecological patterns and useful to disentangle the complex mechanisms that drive them.
A FACT-ETS-1 Antiviral Response Pathway Restricts Viral Replication and is Countered by Poxvirus A51R Proteins
Authors: Rex Emily A. , Seo Dahee , Chappidi Sruthi , Pinkham Chelsea , Oliveira Sabrynna Brito , Embry Aaron , Heisler David , Liu Yang , Luger Karolin , Alto Neal M. , da Fonseca Flávio Guimarães , Orchard Robert , Hancks Dustin , Gammon Don B. 
Published: February 2023

AbstractThe FACT complex is an ancient chromatin remodeling factor comprised of Spt16 and SSRP1 subunits that regulates specific eukaryotic gene expression programs. However, whether FACT regulates host immune responses to infection was unclear. Here, we identify an antiviral pathway mediated by FACT, distinct from the interferon response, that restricts poxvirus replication. We show that early viral gene expression triggers nuclear accumulation of specialized, SUMOylated Spt16 subunits of FACT required for expression of ETS-1, a downstream transcription factor that activates a virus restriction program. However, poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting SSRP1 for binding to SUMOylated Spt16 in the cytosol and by tethering SUMOylated Spt16 to microtubules. Moreover, we show that A51R antagonism of FACT enhances both poxvirus replication in human cells and viral virulence in mice. Finally, we demonstrate that FACT also restricts unrelated RNA viruses, suggesting a broad role for FACT in antiviral immunity. Our study reveals theFACT-ETS-1AntiviralResponse (FEAR) pathway to be critical for eukaryotic antiviral immunity and describes a unique mechanism of viral immune evasion.
Real-time spectral library matching for sample multiplexed quantitative proteomics
Authors: McGann Chris D. , Barshop Will , Canterbury Jesse , Lin Chuwei , Gabriel Wassim , Wilhelm Mathias , McAlister Graeme , Schweppe Devin K. 
Published: February 2023

AbstractSample multiplexed quantitative proteomics has proved to be a highly versatile means to assay molecular phenotypes. Yet, stochastic precursor selection and precursor co-isolation can dramatically reduce the efficiency of data acquisition and quantitative accuracy. To address this, intelligent data acquisition (IDA) strategies have recently been developed to improve instrument efficiency and quantitative accuracy for both discovery and targeted methods. Towards this end, we sought to develop and implement a new real-time library searching (RTLS) workflow that could enable intelligent scan triggering and peak selection within milliseconds of scan acquisition. To ensure ease of use and general applicability, we built an application to read in diverse spectral libraries and file types from both empirical and predicted spectral libraries. We demonstrate that RTLS methods enable improved quantitation of multiplexed samples, particularly with consideration for quantitation from chimeric fragment spectra. We used RTLS to profile proteome responses to small molecule perturbations and were able to quantify up to 15% more significantly regulated proteins in half the gradient time as traditional methods. Taken together, the development of RTLS expands the IDA toolbox to improve instrument efficiency and quantitative accuracy in sample multiplexed analyses.
Breast adipose tissue-derived extracellular vesicles from women with obesity stimulate mitochondrial-induced dysregulated tumor cell metabolism
Authors: Liu Shuchen , Benito-Martin Alberto , Pelissier Vatter Fanny A. , Hanif Sarah Z. , Liu Catherine , Bhardwaj Priya , Sethupathy Praveen , Farghli Alaa R. , Piloco Phoebe , Paik Paul , Mushannen Malik , Otterburn David M. , Cohen Leslie , Bareja Rohan , Krumsiek Jan , Cohen-Gould Leona , Calto Samuel , Spector Jason A. , Elemento Olivier , Lyden David , Brown Kristy A. 
Published: February 2023

AbstractBreast adipose tissue is an important contributor to the obesity-breast cancer link. Dysregulated cell metabolism is now an accepted hallmark of cancer. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we found that long-term education of breast cancer cells (MCF7, T47D) with EVs from breast adipose tissue of women who are overweight or obese (O-EVs) leads to sustained increased proliferative potential. RNA-Seq of O-EV-educated cells demonstrates increased expression of genes, such as ATP synthase and NADH: ubiquinone oxidoreductase, involved in oxidative phosphorylation. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. Mitochondrial complex I inhibitor, metformin, reverses O-EV-induced cell proliferation. Several miRNAs, miR-155-5p, miR-10a-3p, and miR-30a-3p, which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the Akt/mTOR/P70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing the metabolic reprogramming of ER+ breast cancer cells.
Does Music Training Improve Inhibition Control in Children? A Systematic Review and Meta-Analysis
Authors: Jamey Kevin , Foster Nicholas E. V. , Hyde Krista L. , Dalla Bella Simone 
Published: February 2023

AbstractInhibition control is an essential executive function during children’s development, underpinning self-regulation and the acquisition of social and language abilities. This executive function is intensely engaged in music training while learning an instrument, a complex multisensory task requiring monitoring motor performance and auditory stream prioritization. This novel meta-analysis examined music-based training on inhibition control in children. Records from 1980 to 2023 yielded 22 longitudinal studies with controls (N = 1734), including 8 RCTs and 14 others. A random-effects meta-analysis showed that music training improved inhibition control (medium ES) in the RCTs and the superset of twenty-two longitudinal studies (small-to-medium ES). Music training plays a privileged role compared to other activities (sports, visual arts, drama) in improving children’s executive functioning, with a particular effect on inhibition control. We recommend music training for complementing education and as a clinical tool focusing on inhibition control remediation (e.g., in autism and ADHD).
Signal Integration and Adaptive Sensory Diversity Tuning inEscherichia coliChemotaxis
Authors: Moore Jeremy Philippe , Kamino Keita , Kottou Rafaela , Shimizu Thomas , Emonet Thierry 
Published: February 2023

SummaryIn uncertain environments, phenotypic diversity can be advantageous for survival. However, as the environmental uncertainty decreases, the relative advantage of having diverse phenotypes decreases. Here, we show how populations of E. coli integrate multiple chemical signals to adjust sensory diversity in response to changes in the prevalence of each ligand in the environment. Measuring kinase activity in single cells, we quantified the sensitivity distribution to various chemoattractants in different mixtures of background stimuli. We found that when ligands bind uncompetitively, the population tunes sensory diversity to each signal independently, decreasing diversity when the signal ambient concentration increases. However, amongst competitive ligands the population can only decrease sensory diversity one ligand at a time. Mathematical modeling suggests that sensory diversity tuning benefitsE. colipopulations by modulating how many cells are committed to tracking each signal proportionally as their prevalence changes.
LINKIN-associated proteins necessary for tissue integrity during collective cell migration
Authors: Tan Chieh-Hsiang , Cheng Kai-Wen , Park Heenam , Chou Tsui-Fen , Sternberg Paul W. 
Published: February 2023

AbstractCell adhesion plays essential roles in almost every aspect of metazoan biology. LINKIN (Human: ITFG1,Caenorhabditis elegans:lnkn-1) is a conserved transmembrane protein that has been identified to be necessary for tissue integrity during migration. InC. elegans, loss oflnkn-1results in the detachment of the lead migratory cell from the rest of the developing male gonad. Previously, three interactors of ITFG1/lnkn-1– RUVBL1/ruvb-1, RUVBL2/ruvb-2, and alpha-tubulin – were identified by immunoprecipitation-mass spectrometry (IP-MS) analysis using human HEK293T cells and then validated in the nematode male gonad. The ITFG1-RUVBL1 interaction has since been independently validated in a breast cancer cell line model that also implicates the involvement of the pair in metastasis. Here, we showed that epitope-tagged ITFG1 localized to the cell surface of MDA-MB-231 breast cancer cells. Using IP-MS analysis, we identified a new list of potential interactors of ITFG1.Loss-of-functionanalysis of theirC. elegansorthologs found that three of the interactors – ATP9A/tat-5, NME1/ndk-1, and ANAPC2/apc-2– displayed migratory detachment phenotypes similar to that oflnkn-1. Taken together with the other genes whose reduction-of-function phenotype is similar to that oflnkn-1(notably cohesion and condensin), suggests the involvement of membrane remodeling and chromosome biology in LINKIN-dependent cell adhesion and supports the hypothesis for a structural role of chromosomes in post-mitotic cells.
Spotty distributions: Spotted Gar (Lepisosteus oculatus) and Spotted Sucker (Minytrema melanops) range expansion in eastern Lake Erie
Authors: MacGuigan Daniel J. , Porto-Hannes Isabel , Foote Brian , Backenstose Nathan J. C. , Osborne Christopher , Louisor Kimberly , Waterman Hannah , Chang Sarah L. , Cochran Jacob L. , Krabbenhoft Trevor J. 
Published: February 2023

ABSTRACTNatural range expansions in warm-water freshwater fishes are currently not well understood, but shifts in native species distributions can be influenced by many factors, including habitat restoration or degradation and climate change. Here, we provide empirical evidence of range expansions observed in two native freshwater fish species in Lake Erie: the Spotted Gar (Lepisosteus oculatus)and Spotted Sucker (Minytrema melanops). We confirmed our field identifications ofL. oculatusandM. melanopsusing mtDNA barcoding. Maximum likelihood phylogenetic analyses reveal that our samples confidently resolve in theL. oculatusandM. melanopsclades respectively, with additional identification support from BLAST searches. Notably, we found no correlation between the increased detection rate of both species and an increase in sampling effort when compared to previous records. Historically, eastern Lake Erie experienced habitat degradation through channelization, siltation, dredging, and toxification of sediments. We hypothesize that recent habitat remediation efforts have provided suitable habitat for both species to recolonize shallow waters with densely vegetated habitat (>90% substrate coverage). Both species are likely to continue their northern expansion as habitats are restored and climatic changes favor warm-water fishes.
The origins and diversification of Holarctic brown bear populations inferred from genomes of past and present populations
Authors: Segawa Takahiro , Rey-Iglesia Alba , Lorenzen Eline D , Westbury Michael V 
Published: February 2023

AbstractThe brown bear (Ursus arctos) is one of the survivors of the Late Quaternary megafauna extinctions. However, despite being widely distributed across the Holarctic, brown bears have experienced extensive range reductions, and even extirpations in some geographic regions. Previous research efforts utilising genetic data have provided valuable insights into their evolutionary history. However, most studies have been limited to contemporary individuals or mitochondrial DNA, limiting insights into population processes that preceded the present. Here we present genomic data from two Late Pleistocene brown bears from Honshu, Japan, and eastern Siberia, and combine them with published contemporary and ancient genomes from across the Holarctic range of brown bears to investigate the evolutionary relationships among brown bear populations through time and space. By including genomic data from Late Pleistocene and Holocene individuals sampled outside the current distribution range we uncover diversity not present in the contemporary populations. Notably, although contemporary individuals display geographically structured populations most likely driven by isolation-by-distance, this pattern varies among the ancient samples across different regions. The inclusion of ancient brown bears in our analysis provides novel insights into the evolutionary history of brown bears and contributes to understanding the populations and diversity lost during the Late Quaternary.
Root associated bacterial communities and root metabolite composition are linked to nitrogen use efficiency in sorghum
Authors: Chai Yen Ning , Qi Yunhui , Goren Emily , Sheflin Amy M. , Tringe Susannah , Prenni Jessica E. , Liu Peng , Schachtman Daniel 
Published: February 2023

AbstractDevelopment of cereal crops with high nitrogen-use efficiency (NUE) is a priority for worldwide agriculture. In addition to conventional plant breeding and genetic engineering, the use of the plant microbiome offers another approach to improve crop NUE. To gain insight into the bacterial communities associated with sorghum lines that differ in NUE, a field experiment was designed comparing 24 diverse sorghum lines under sufficient and deficient nitrogen (N). Amplicon sequencing and untargeted gas chromatography-mass spectrometry (GC-MS) were used to characterize the bacterial communities and the root metabolome associated with sorghum genotypes varying in sensitivity to low N. We demonstrated that N stress and sorghum type (energy, sweet, and grain sorghum) significantly influenced the root-associated bacterial communities and root metabolite composition of sorghum. Sorghum NUE was positively correlated with the bacterial richness and diversity in the rhizosphere. The greater alpha diversity in high NUE lines was associated with the decreased abundance of a dominant bacterial taxa,Pseudomonas. Multiple strong correlations were detected between root metabolites and rhizosphere bacterial communities in response to N stress and indicate that the shift in the sorghum microbiome due to low-N is associated with the root metabolites of the host plant. Taken together, our study provides new insight into the links between host genetic regulation of root metabolites and root-associated microbiome of sorghum genotypes differing in NUE and tolerance to low-N stress.