bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational modeling of posteroanterior lumbar traction by an automated massage bed: predicting intervertebral disc stresses and deformation
Authors: Cardoso Luis , Khadka Niranjan , Dmochowski Jacek , Meneses Edson , Jin Youngsoo , Bikson Marom 
Published: May 2022

AbstractSpinal traction is a physical intervention that provides constant or intermittent stretching axial force to the lumbar vertebrae to gradually distract spinal tissues into better alignment, reduce intervertebral disc (IVD) pressure, and manage lower back pain (LBP). However, such axial traction may change the normal lordotic curvature, and result in unwanted side effects and/or inefficient reduction of the IVD pressure. An alternative to axial traction has been recently tested, consisting of posteroanterior (PA) traction in supine posture, which was recently shown effective to increase the intervertebral space and lordotic angle using MRI. PA traction aims to maintain the lumbar lordosis curvature throughout the spinal traction therapy while reducing the intradiscal pressure. In this study, we developed finite element simulations of mechanical therapy produced by a commercial thermo-mechanical massage bed capable of spinal PA traction. The stress relief produced on the lumbar discs by the posteroanterior traction system was investigated on human subject models with different BMI (normal, overweight, moderate obese and extreme obese BMI cases). We predict typical traction levels lead to significant distraction stresses in the lumbar discs, thus producing a stress relief by reducing the compression stresses normally experienced by these tissues. Also, the stress relief experienced by the lumbar discs was effective in all BMI models, and it was found maximal in the normal BMI model. These results are consistent with prior observations of therapeutic benefits derived from spinal AP traction.
Identification of Dynamic Microbial Signatures in Longitudinal Studies
Authors: Calle M.Luz , Susin Antoni 
Published: May 2022

AbstractThe study of microbiome dynamics is key for unveiling the role of the microbiome in human health. Addressing the compositional structure of microbiome data is particularly critical in longitudinal studies where compositions measured at different times can yield to different subcompositions.We propose a new compositional data analysis (CoDA) algorithm for inferring dynamic microbial signatures. The algorithm performs penalized regression over the summary of the log-ratio trajectories (the area under these trajectories) and the inferred microbial signature is expressed as a log-contrast model. Graphical representations of the results are provided to facilitate the interpretation of the analysis: plot of the log-ratio trajectories, plot of the signature and plot of the prediction accuracy of the model. The new proposal is illustrated with data on the developing microbiome of infants.The algorithm is implemented in the R package “code4microbiome” (https://cran.r-project.org/web/packages/coda4microbiome/) that is accompanied with a vignette with a detailed description of the functions. The website of the project contains several tutorials: https://malucalle.github.io/coda4microbiome/
Huntington’s Disease Produces Multiplexed Transcriptional Vulnerabilities of Striatal D1-D2 and Striosome-Matrix Neurons
Authors: Matsushima Ayano , Pineda Sergio Sebastian , Crittenden Jill R. , Lee Hyeseung , Galani Kyriakitsa , Mantero Julio , Kellis Manolis , Heiman Myriam , Graybiel Ann M. 
Published: May 2022

AbstractStriatal cell-type-specific vulnerability in Huntington’s disease (HD) preferentially affects dopamine D2R-expressing projection neurons (SPNs), compatible with manifest motor symptomatology in HD. Transcriptional studies of striatal striosome-matrix compartmentalization in HD are, however, limited, despite pathologic evidence for striosome vulnerability aligning with early mood symptomatology. We used single-nucleus RNA-sequencing on striatal samples from two murine models, and rare Grade 1 HD patient tissues, to examine striosome and matrix sub-clusters within parent D1 and D2 SPN clusters. In human HD, striosomal SPNs were the most depleted SPN population. Surprisingly, for both mouse models, transcriptomic distinctiveness was diminished more for striosome-matrix SPNs than for D1-D2 SPNs. Compartmental markers were dysregulated so as to cancel endogenous identities as striosomal or matrix SPNs, but markers for D1-D2 exhibited less identity obscuring. The canonical striosome-matrix as well as D1-D2 organizations of the striatum thus are both strongly, but differentially, compromised in HD and are targets for therapeutics.
Biophysical, Molecular and Proteomic profiling of Human Retinal Organoids derived Exosomes
Authors: Arthur Peggy , Kandoi Sangeetha , Sun Li , Kalvala Anil , Kutlehria Shallu , Bhattacharya Santanu , Kulkarni Tanmay , Nimma Ramesh , Li Yan , Lamba Deepak A. , Singh Mandip 
Published: May 2022

AbstractExtracellular vesicles (EVs) are phospholipid bilayer-bound particles released by cells that play a role in cell-cell communication, signal transduction, and extracellular matrix remodeling. There is a growing interest in EVs for ocular applications as therapeutics, biomarkers, and drug delivery vehicles. EVs secreted from mesenchymal stem cells (MSCs) have shown to provide therapeutic benefits in ocular conditions. However, very little is known about the properties of bioreactors cultured-3D human retinal organoids secreted EVs. This study provides a comprehensive morphological, nanomechanical, molecular, and proteomic characterization of retinal organoid EVs and compares it with human umbilical cord (hUC) MSCs. Nanoparticle tracking analysis indicated the average size of EV as 100–250 nm. Atomic force microscopy showed that retinal organoid EVs are softer and rougher than the hUCMSC EVs. Gene expression analysis by qPCR showed a high expression of exosome biogenesis genes in late retinal organoids derived EVs (>120 days). Immunoblot analysis showed highly expressed exosomal markers Alix, CD63, Flotillin-2, HRS and Hsp70 in late retinal organoids compared to early retinal organoids EVs (<120 days). Protein profiling of retinal organoid EVs displayed a higher differential expression of retinal function-related proteins and EV biogenesis/marker proteins than hUCMSC EVs, implicating that the use of retinal organoid EVs may have a superior therapeutic effect on retinal disorders. This study adds supplementary knowledge on the properties of EVs secreted by retinal organoids and suggests their potential use in the diagnostic and therapeutic treatments for ocular diseases.
Spatially-enhanced clusterwise inference for testing and localizing intermodal correspondence
Authors: Weinstein Sarah M. , Vandekar Simon N. , Baller Erica B. , Tu Danni , Adebimpe Azeez , Tapera Tinashe M. , Gur Ruben C. , Gur Raquel E. , Detre John A. , Raznahan Armin , Alexander-Bloch Aaron F. , Satterthwaite Theodore D. , Shinohara Russell T. , Park Jun Young 
Published: May 2022

AbstractWith the increasing availability of neuroimaging data from multiple modalities—each providing a different lens through which to study brain structure or function—new techniques for comparing, integrating, and interpreting information within and across modalities have emerged. Recent developments include hypothesis tests of associations between neuroimaging modalities, which can be used to determine the statistical significance of intermodal associations either throughout the entire brain or within anatomical subregions or functional networks. While these methods provide a crucial foundation for inference on intermodal relationships, they cannot be used to answer questions about where in the brain these associations are most pronounced. In this paper, we introduce a new method, called CLEAN-R, that can be used both to test intermodal correspondence throughout the brain and also to localize this correspondence. Our method involves first adjusting for the underlying spatial autocorrelation structure within each modality before aggregating information within small clusters to construct a map of enhanced test statistics. Using structural and functional magnetic resonance imaging data from a subsample of children and adolescents from the Philadelphia Neurodevelopmental Cohort, we conduct simulations and data analyses where we illustrate the high statistical power and nominal type I error levels of our method. By constructing an interpretable map of group-level correspondence using spatially-enhanced test statistics, our method offers insights beyond those provided by earlier methods.
Preterm infants show an atypical processing of the mother’s voice
Authors: Filippa Manuela , Benis Damien , Adam-Darque Alexandra , Grandjean Didier , Huppi Petra S. 
Published: May 2022

AbstractTo understand the consequences of prematurity on language perception it is fundamental to determine how atypical early sensory experience affects brain development. To date the neural oscillatory correlates in the time-frequency domain of voice processing as a function of atypical early sensory experience, as after premature birth, remain elusive. At term equivalent age, ten preterm and ten full-term newborns underwent high-density EEG recordings during mother or stranger speech presentation, presented in the forward (naturalistic) or backward order. A general group effect terms > preterms for the naturalistic mother’s voice is evident in the theta frequency band in the left temporal area, where only full-term newborns showed an increased activity for the mother’s voice, whereas preterm infants showed significant activation for stranger naturalistic speech. Similarly, a significant group contrast in the low and high theta in the right temporal regions indicates higher activations for the stranger’s speech in preterms. Finally, only full-term newborns presented a late gamma band increase for the maternal naturalistic speech, indicating a more mature brain response.The current study based on neural time-frequency patterns, demonstrates that preterm infants lack selective brain responses to mother’s naturalistic voice typical for full-term newborns, whereas preterms are selectively responsive to stranger voices in both temporal hemispheres.
Mechanochemical signal transduction in synthetic cells
Authors: Jahnke Kevin , Illig Maja , Scheffold Marlene , Tran Mai P. , Mersdorf Ulrike , Göpfrich Kerstin 
Published: May 2022

AbstractMechanotransduction determines the adaptive response of natural cells via transmem-brane proteins1. The incorporation of membrane-spanning structures to guide cellular function and to enable transmembrane signalling is therefore a critical aim for bottom-up synthetic biology2,3,4. Here, we design membrane-spanning DNA origami signalling units (DOSUs) and mechanically couple them to DNA cytoskeletons5 encapsulated within giant unilamellar vesicles (GUVs). We verify the assembly and incorporation of the DOSUs into the GUV membranes and achieve their clustering upon external stimulation. The transmembrane-spanning DOSUs act as a pore to allow for the transport of single-stranded DNA into the GUVs. We employ this to externally trigger the reconfiguration of DNA cytoskeletons within GUVs using strand displacement reactions. In addition to chemical signalling, we achieve the mechanical coupling of the externally added DOSUs and the internal DNA cytoskeletons. We induce clustering of the DOSUs, which triggers a symmetry break in the organization of the DNA cytoskeleton which is mechanically coupled to the DOSU.Our work thus provides a mechanical and chemical transmembrane signaling module towards the assembly of stimuli-responsive and adaptive synthetic cells.
Shuffled ATG8 interacting motifs form an ancestral bridge between UFMylation and C53-mediated autophagy
Authors: Picchianti Lorenzo , de Medina Hernández Víctor Sánchez , Zhan Ni , Irwin Nicholas A. T. , Stephani Madlen , Hornegger Harald , Beveridge Rebecca , Sawa-Makarska Justyna , Lendl Thomas , Grujic Nenad , Martens Sascha , Richards Thomas A. , Clausen Tim , Ramundo Silvia , Karagöz G. Elif , Dagdas Yasin 
Published: May 2022

AbstractUFMylation mediates the covalent modification of substrate proteins with UFM1 (Ubiquitin-fold modifier 1) and regulates the selective degradation of endoplasmic reticulum (ER) via autophagy (ER-phagy) to maintain ER homeostasis. Specifically, collisions of the ER-bound ribosomes trigger ribosome UFMylation, which in turn activates C53-mediated autophagy that clears the toxic incomplete polypeptides. C53 has evolved non-canonical shuffled ATG8 interacting motifs (sAIMs) that are essential for ATG8 interaction and autophagy initiation. Why these non-canonical motifs were selected during evolution, instead of canonical ATG8 interacting motifs remains unknown. Here, using a phylogenomics approach, we show that UFMylation is conserved across the eukaryotes and secondarily lost in fungi and some other species. Further biochemical assays have confirmed those results and showed that the unicellular algae,Chlamydomonas reinhardtiihas a functional UFMylation machinery, overturning the assumption that this process is linked to multicellularity. Our conservation analysis also revealed that UFM1 co-evolves with the sAIMs in C53, reflecting a functional link between UFM1 and the sAIMs. Using biochemical and structural approaches, we confirmed the interaction of UFM1 with the C53 sAIMs and found that UFM1 and ATG8 bound to the sAIMs in a different mode. Conversion of sAIMs into canonical AIMs prevented binding of UFM1 to C53, while strengthening ATG8 interaction. This led to the autoactivation of the C53 pathway and sensitizedArabidopsis thalianato ER stress. Altogether, our findings reveal an ancestral toggle switch embodied in the sAIMs that regulates C53-mediated autophagy to maintain ER homeostasis.
Mutational impact of APOBEC3A and APOBEC3B in a human cell line and comparisons to breast cancer
Authors: Carpenter Michael A. , Temiz Nuri A. , Ibrahim Mahmoud A. , Jarvis Matthew C. , Brown Margaret R. , Argyris Prokopios P. , Brown William L. , Yee Douglas , Harris Reuben S. 
Published: May 2022

AbstractA prominent source of mutation in cancer is single-stranded DNA cytosine deamination by cellular APOBEC3 enzymes, which results in signature C-to-T and C-to-G mutations in TCA and TCT motifs. Although multiple enzymes have been implicated, reports conflict and it is unclear which protein(s) are responsible. Here we report the development of a selectable system to quantify genome mutation and demonstrate its utility by comparing the mutagenic activities of three leading candidates - APOBEC3A, APOBEC3B, and APOBEC3H. The human cell line, HAP1, is engineered to express thethymidine kinase(TK) gene of HSV-1, which confers sensitivity to ganciclovir. Expression of APOBEC3A and APOBEC3B, but not catalytic mutant controls or APOBEC3H, triggers increased frequencies ofTKmutation and nearly indistinguishable TC-biased cytosine mutation profiles in the selectableTKreporter gene. Whole genome sequences fromTKmutant clones enabled an analysis of thousands of single base substitution mutations and extraction of local sequence preferences with APOBEC3A preferring YTCW motifs over 70% of the time and APOBEC3B just under 50% of the time (Y=C/T; W=A/T). Signature comparisons with breast tumor whole genome sequences indicate that most malignancies manifest intermediate percentages of APOBEC3 signature mutations in YTCW motifs, mostly between 50 and 70%, suggesting that both enzymes are contributing in a combinatorial manner to the overall mutation landscape. Although the vast majority of APOBEC3A- and APOBEC3B-induced single base substitution mutations occur outside of predicted chromosomal DNA hairpin structures, whole genome sequence analyses and supporting biochemical studies also indicate that both enzymes are capable of deaminating the single-stranded loop regions of DNA hairpins at elevated rates relative to control conditions. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both APOBEC3A and APOBEC3B.
SWAP1-SFPS-RRC1 splicing factor complex modulates pre-mRNA splicing to promote photomorphogenesis in Arabidopsis
Authors: Kathare Praveen Kumar , Xin Ruijiao , Ganesan Abirama Sundari , June Viviana M. , Reddy Anireddy S. N. , Huq Enamul 
Published: May 2022

ABSTRACTLight signals perceived by a group of photoreceptors have profound effects on the physiology, growth, and development of plants. The red/far-red light absorbing phytochromes modulate these aspects by intricately regulating gene expression at multiple levels. Previously, we reported that two splicing factors SFPS (SPLICING FACTOR FOR PHYTOCHROME SIGNALING) and RRC1 (REDUCED RED LIGHT RESPONSES IN CRY1CRY2 BACKGROUND 1), interact with photoactivated phyB to regulate light-mediated pre-mRNA alternative splicing (AS). Here, we report the identification and functional characterization of an RNA binding splicing factor, SWAP1 (SUPPRESSOR-OF-WHITE-APRICOT/SURP RNA-BINDING DOMAIN-CONTAINING PROTEIN1). Loss-of-function swap1-1 mutant is hyposensitive to red light and exhibits a day light-independent early flowering phenotype. SWAP1 physically interacts with both SFPS and RRC1 in a light-independent manner and forms a ternary complex. In addition, SWAP1 also physically interacts with photoactivated phyB and colocalizes with nuclear phyB photobodies. Deep RNA-seq analyses show that SWAP1 regulates the gene expression and pre-mRNA alternative splicing of a large number of genes including those involved in plant responses to light signaling. A comparison with SFPS- and RRC1-regulated events shows that all three splicing factors coordinately regulate the alternative splicing of a subset of genes. Collectively, our study uncovered the function of a new splicing factor, which interacts with photoactivated phyB, in modulating light-regulated development in plants.SIGNIFICANCERegulation of transcription and pre-mRNA alternative splicing is essential for the transcript diversity and modulation of light signaling in plants. Although several transcription factors involved in light signaling have been discovered and characterized in-depth, only a few splicing factors have been shown to be involved in the regulation of light signaling pathways. In this study, we describe the identification and characterization of a new splicing factor SWAP1, which interact with two previously characterized splicing factors, SFPS and RRC1, forming a ternary complex. We show that, like SFPS and RRC1, SWAP1 also interacts with photoactivated phyB, and consistently, swap1 seedlings are hyposensitive to red light. SWAP1 modulates alternative splicing of a large number of genes and a subset of these genes are coordinately regulated by SFPS, RRC1 and SWAP1. These results highlight the importance of not only the transcription factors but also the phyB-interacting splicing factors in light-regulated plant development.
Pseudomonas aeruginosa Elicits Sustained IL-1β Upregulation in Alveolar Macrophages from Lung Transplant Recipients
Authors: Britton Noel , Villabona-Rueda Andres , Whiteside Samantha A. , Mathew Joby , Kelley Matthew , Agbor-Enoh Sean , McDyer John , Christie Jason D. , Collman Ronald G. , Cox Andrea , Shah Pali , D’Alessio Franco 
Published: May 2022

AbstractBackgroundIsolation of Pseudomonas aeruginosa (PsA) is associated with increased BAL (bronchoalveolar lavage) inflammation and lung allograft injury in lung transplant recipients (LTR). However, the effect of PsA on macrophage responses in this population is incompletely understood. We examined human alveolar macrophage (AM) responses to PsA and Pseudomonas dominant microbiome in healthy lung transplant recipients (LTR).MethodsWe stimulated THP-1 derived macrophages (THP-1M) and human AM from LTR with different bacteria and LTR BAL derived microbiome characterized as Pseudomonas-dominant. Macrophage responses were assessed by high dimensional flow cytometry, including their intracellular production of cytokines (TNF-α, IL-6, IL-8, IL-1β, IL-10, IL-1RA, and TGF-β). Pharmacological inhibitors were utilized to evaluate the role of the inflammasome in PsA-macrophages interaction.ResultsWe observed upregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-8, IL-1β) following stimulation by PsA compared to other bacteria (Staphylococcus aureus, Prevotella melaninogenica, Streptococcus pneumoniae) in both THP-1 derived and LTR AM, predominated by IL-1β. IL-1β production from THP-1 was sustained after PsA stimulation for up to 96 hours and 48 hours in LTR AM. Treatment with the inflammasome inhibitor BAY11-7082 abrogated macrophage IL-1β and IL-18 production after PsA exposure. BAL Pseudomonas-dominant microbiota elicited an increased IL-1β, similar to PsA, an effect abrogated by the addition of antibiotics.ConclusionPsA and PsA-dominant lung microbiota induce sustained IL-1β production in LTR AM. Pharmacological targeting of the inflammasome reduces PsA-macrophage-IL1β responses, underscoring their use in lung transplant recipients.
p75NTR prevents the onset of cerebellar granule cell migration via RhoA activation
Authors: Zanin Juan P. , Friedman Wilma J. 
Published: May 2022

SummaryNeuronal migration is one of the fundamental processes during brain development. Several neurodevelopmental disorders can be traced back to dysregulated migration. Although substantial efforts have been placed in identifying molecular signals that stimulate migration, little is known about potential mechanisms that restrict migration. These restrictive mechanisms are essential for proper development since it helps coordinate the timing for each neuronal population to arrive and establish proper connections. Moreover, preventing migration away from a proliferative niche is necessary to maintain a pool of proliferating cells until the proper number of neuronal progenitors is attained.Here, we identify an anti-migratory role for the p75 neurotrophin receptor (p75NTR) in cerebellar development. Our results show that granule cell precursors robustly express p75NTR in the external granule layer (EGL) when they are proliferating during postnatal development, however, they do not express p75NTR when they migrate either from the rhombic lip during embryonic development or from the EGL during postnatal development. We show that p75NTR prevented GCP migration by maintaining elevated levels of active RhoA. The expression of p75NTR was sufficient to prevent the migration of the granule cells even in the presence of BDNF, a well-established chemotactic signal for this cell population. Our findings suggest that the expression of p75NTR might be a critical signal that stops and maintains the GCPs in the proliferative niche of the EGL, promoting the clonal expansion of cerebellar granule neurons.
Musashi1 and its short C-terminal variants regulate pluripotency states in embryonic stem cells
Authors: Chen Youwei , Zhang Hailin , Han Jiazhen , Li Qianyan , Chen Ying , Lin Gufa 
Published: May 2022

ABSTRACTMusashi1 (MSI1) is a marker for adult stem cells, but little is known for its expression and function in pluripotent stem cells (PSCs). Here we report that MSI1 is expressed in embryonic stem cells (ESCs) and is required for pluripotency maintenance. We found that there exit short c-terminal MSI1 variants (MSI1-C, hMSI1272-362 or mMSI1138-362) in naïve but not primed ESCs. When overexpressed, MSI1 and MSI1-C variants facilitate primed-to-naïve pluripotency transition by elevating the pluripotency of primed hESCs toward a formative-like state, enable better survival of hESCs in human-mouse interspecies cell completion, and enhance the ability of blastoid formation of hESCs after naïve induction. Mechanistically, we show that the MSI1-C variants, though lacking RNA recognition motifs, bind to RNAs, enhance stress resistance and upregulate DNA damage repair genes. Thus, this study demonstrates that ESCs utilize MSI1 and the newly identified short MSI1-C proteins as double swords to regulate pluripotency states.