bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rose flavor compound activating the NRF2 pathway in dendritic cells ameliorates contact hypersensitivity in mice
Authors: Kodama Naoki , Okada Hikaru , Hachisu Masakazu , Ando Miki , Ito Naoto , Nagata Kazuki , Yasuda Yayoi , Hiroki Ikumi , Yashiro Takuya , Ichihara Gaku , Yamamoto Masayuki , Nishiyama Chiharu 
Published: February 2022

AbstractDendritic cells (DCs), which are typical antigen-presenting cells, localize to various sites in the body, particularly the front line of infection as sentinels, and are involved in innate and adaptive immune responses. Although the functions of DCs, such as pathogen-induced cytokine production and antigen-specific T cell activation, are important for host defenses against infection and tumorigenesis, the hyper- and/or extended activation of DCs leads to inflammatory and autoimmune diseases. In the present study, β-damascone, a major ingredient of rose fragrance, was selected from an aroma library as a candidate compound that suppresses antigen-induced immune responses. β-Damascone inhibited the functions of DCs, including the antigen-dependent proliferation of T cells, DC-induced Th1 development, and the TLR ligand-induced production of inflammatory cytokines by DCs. The β-damascone treatment also increased the protein level of the transcription factor NRF2, which plays key roles in antioxidant responses, and the transcription ofHmox1, a target gene of NRF2, in DCs.Nrf2−/−DCs induced Th1-development and produced large amount of IL-12p40 even in the presence of β-damascone, whereas these functions byNrf2+/−DCs were inhibited by β-damascone under the same conditions. The intake of β-damascone suppressed ear swelling in contact hypersensitivity (CHS) model mice, but not in CHS-inducedNrf2−/−mice. Collectively, the present results indicate the potential of the rose aroma compound β-damascone, which suppresses DC-mediated immune responses by activating the NRF2 pathway in DCs, for the prevention and/or attenuation of immune-mediated diseases.
Comparing dormancy in two distantly related tunicates reveals morphological, molecular, and ecological convergences and repeated co-option
Authors: Hiebert Laurel S. , Scelzo Marta , Alié Alexandre , De Tomaso Anthony , Brown Federico , Tiozzo Stefano 
Published: February 2022

AbstractMany asexually-propagating marine invertebrates can survive extreme environmental conditions by developing dormant structures, i.e., morphologically simplified bodies that retain the capacity to completely regenerate a functional adult when conditions return to normal. Here, we examine the environmental, morphological, and molecular characteristics of dormancy in two distantly related clonal tunicate species: Polyandrocarpa zorritensis and Clavelina lepadiformis. In both species, we report that the dormant structures are able to withstand harsher temperature and salinity conditions compared to the adult, and are the dominant forms these species employ to survive the colder winter months. By finely controlling the entry and exit of dormancy in laboratory-reared individuals, we were able to select and characterize the morphology of dormant structures associated with their transcriptome dynamics. In both species, we identified putative stem and nutritive cells in structures that resemble the earliest stages of asexual propagation. By characterizing gene expression during dormancy and regeneration into the adult body plan (i.e., germination), we observed that genes which control dormancy and environmental sensing in other metazoans, notably HIF-α and insulin signaling genes, are also expressed in tunicate dormancy. Germination-related genes in these two species, such as the retinoic acid pathway, are also found in other unrelated clonal tunicates during asexual development. These results are suggestive of repeated exaptation of conserved eco-physiological and regeneration programs for the origin of novel dormancy-germination processes across distantly related animal taxa.
Impacts of Spaceflight Experience on Human Brain Structure
Authors: McGregor Heather R. , Hupfeld Kathleen E. , Pasternak Ofer , Beltran Nichole E. , Dios Yiri E. De , Bloomberg Jacob J. , Wood Scott J. , Mulavara Ajitkumar P. , Riascos Roy F. , Reuter-Lorenz Patricia A. , Seidler Rachael D. 
Published: February 2022

AbstractSpaceflight induces widespread changes in human brain morphology. It is unclear if these brain changes differ with varying mission durations or one’s history of spaceflight experience (e.g., number of prior missions, time between missions). Here we addressed this issue by quantifying voxelwise post-flight changes in gray matter volume, white matter microstructure, extracellular free water (FW), and ventricular volume in a sample of 28 astronauts. We found that longer missions induced greater ventricular expansion and larger FW displacement at the top of the brain. A greater number of prior missions was associated with white matter microstructure declines in a tract supporting voluntary leg movement. Longer inter-mission intervals were associated with greater ventricle expansion, with compensatory ventricular expansion observed only in those crewmembers with inter-missions intervals of 3 years or longer. Longer missions therefore induce more extensive brain fluid shifts, and the ventricles may require at least 3 years to recover post-flight.
Depletion of the RNA-binding protein PURA triggers changes in posttranscriptional gene regulation and loss of P-bodies
Authors: Molitor Lena , Klostermann Melina , Bacher Sabrina , Merl-Pham Juliane , Spranger Nadine , Burczyk Sandra , Ketteler Carolin , Rusha Ejona , Tews Daniel , Pertek Anna , Proske Marcel , Busch Anke , Reschke Sarah , Feederle Regina , Hauck Stefanie M. , Blum Helmut , Drukker Micha , Fischer-Posovszky Pamela , König Julian , Zarnack Kathi , Niessing Dierk 
Published: February 2022

AbstractThe RNA-binding protein PURA has been implicated in the rare, monogenetic, neurodevelopmental disorder PURA Syndrome. PURA binds both DNA and RNA and has been associated with various cellular functions. Only little is known about its main cellular roles and the molecular pathways affected uponPURAdepletion. Here, we show that PURA is predominantly located in the cytoplasm, where it binds to thousands of mRNAs. Many of these transcripts change abundance in response toPURAdepletion. The encoded proteins suggest a role for PURA in immune responses, mitochondrial function, autophagy and processing (P)-body activity. Intriguingly, reduced PURA levels decrease the expression of the integral P-body components LSM14A and DDX6 and strongly affect P-body formation in human cells. Furthermore,PURAknockdown results in stabilization of P-body-enriched transcripts, whereas other mRNAs decrease. Hence, reduced PURA levels, as reported in patients with PURA Syndrome, influence the formation and composition of this phase-separated RNA processing machinery. Our study proposes PURA Syndrome as a new model to study the tight connection between P-body-associated RNA regulation and neurodevelopmental disorders.Graphical Abstract
SPRI: Spatial Pattern Recognition using Information based method for spatial gene expression data
Authors: Hu Jin-Xian , Hu Zhi-Rui , Yuan Ye , Shen Hong-Bin 
Published: February 2022

AbstractThe rapid development of spatially resolved transcriptomics has made it possible to analyze spatial gene expression patterns in complex biological tissues. To identify spatially differential expressed genes, we propose a novel and robust nonparametric information-based approach, SPRI. SPRI converts the problem of identifying spatial gene expression patterns into the detection of dependencies between spatial coordinates with observed frequencies measured by read counts. It directly models spatial transcriptome raw count without assuming a parametric model. SPRI was applied to spatial datasets with different resolutions, suggesting that SPRI outperforms previous methods, by robustly detecting more genes with significant spatial expression patterns, and revealing biological insights that cannot be identified by other methods.
Cerebellar and cortico-striatal-midbrain contributions to reward-cognition processes and apathy within the psychosis continuum
Authors: Bègue Indrit , Brakowski Janis , Seifritz Erich , Dagher Alain , Tobler Philippe N. , Kirschner Matthias , Kaiser Stefan 
Published: February 2022

AbstractNegative symptoms in the psychosis continuum are linked to impairments in reward processing and cognitive function. Processes at the interface of reward processing and cognition and their relation to negative symptoms remain little studied, despite evidence suggestive of integration in mechanisms and neural circuitry. Here, we investigated brain activation during reward-dependent modulation of working memory (WM) and their relationship to negative symptoms in subclinical and early stages of the psychosis continuum. We included 27 persons with high schizotypal personality traits and 23 patients with first episode psychosis as well as 27 healthy controls. Participants underwent functional magnetic resonance imaging while performing an established 2-back WM task with two reward levels (5 CHF vs. no reward), which allowed us to assess common reward-cognition regions through whole-brain conjunction analyses and to investigate relations with clinical scores of negative symptoms. As expected for behavior, reward facilitated performance while cognitive load diminished it. At the neural level, the conjunction of high reward and high cognitive load contrasts across the psychosis continuum showed increased hemodynamic activity in the thalamus and the cerebellar vermis. During high cognitive load, more severe apathy but not diminished expression in the psychosis continuum was associated with reduced activity in right lateral orbitofrontal cortex, midbrain, posterior vermal cerebellum, caudate and lateral parietal cortex. Our results suggest that hypoactivity in the cerebellar vermis and the cortical-striatal-midbrain-circuitry in the psychosis continuum relates to apathy possibly via impaired flexible cognitive resource allocation for effective goal pursuit.
CD8 memory precursor cells generation is a continuous process
Authors: Todorov Helena , Prieux Margaux , Laubreton Daphne , Bouvier Matteo , Wang Shaoying , de Bernard Simon , Arpin Christophe , Cannoodt Robrecht , Saelens Wouter , Bonnaffoux Arnaud , Gandrillon Olivier , Crauste Fabien , Saeys Yvan , Marvel Jacqueline 
Published: February 2022

AbstractIn this work, we studied the generation of memory precursor cells following an acute infection by analyzing single-cell RNA-seq data that contained CD8 T cells collected during the postinfection expansion phase. We used different tools to reconstruct the developmental trajectory that CD8 T cells followed after activation. Cells that exhibited a memory precursor signature were identified and positioned on this trajectory. We found that memory precursors are generated continuously with increasing numbers being generated over time. Similarly, expression of genes associated with effector functions was also found to be raised in memory precursors at later time points. The ability of cells to enter quiescence to differentiate into memory cells was confirmed by BrdU pulse-chase experiment in vivo. Analysis of cell counts indicates that the vast majority of memory cells are generated at later time points from cells that have extensively divided.
Transcriptional regulation and chromatin architecture maintenance are decoupled modular functions at the Sox2 locus
Authors: Taylor Tiegh , Sikorska Natalia , Shchuka Virlana M , Chahar Sanjay , Ji Chenfan , Macpherson Neil N , Moorthy Sakthi D , Mitchell Jennifer A , Sexton Tom 
Published: February 2022

SUMMARYHow distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the Sox2 locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We trace nearly all Sox2 transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter-enhancer interaction frequencies or topological domain organization. Local chromatin architecture maintenance, including at the topologically associating domain (TAD) boundary downstream of the Sox2 enhancer, is widely distributed over multiple transcription factor-bound regions and maintained in a CTCF-independent manner. Furthermore, disruption of promoter-enhancer interactions by ectopic chromatin loop formation has no effect on Sox2 expression. These findings indicate that many transcription factors are involved in modulating chromatin architecture independently of CTCF.
Exotic alleles contribute to heat tolerance in wheat under field conditions
Authors: Molero Gemma , Coombes Benedict , Joynson Ryan , Pinto Francisco , Piñera-Chávez Francisco J. , Rivera-Amado Carolina , Hall Anthony , Reynolds Matthew P 
Published: February 2022

AbstractGlobal warming is one of the most significant threats to food security. With temperatures predicted to rise and extreme weather events becoming more common we must safeguard food production by developing crop varieties that are more tolerant to heat stress without compromising yield under favourable conditions. By evaluating 149 spring wheat lines in the field under yield potential and heat stressed conditions, we demonstrate how strategic integration of exotic material significantly increases yield under heat stress compared to elite lines, with no significant yield penalty under favourable conditions. Genome-wide association analysis revealed three marker trait associations, which together increase yield under heat stress by over 50% compared to lines without the advantageous alleles and was associated with approximately 2°C lower canopy temperature. We identified anAegilops tauschiiintrogression underlying the most significant of these associations. By comparing overlapping recombination of this introgressed segment between lines, we identified a 1.49Mbp region of the introgression responsible for this association that increases yield under heat stress by 32.4%. The genes within this region were extracted from diverseAe. tauschiigenomes, revealing a novelAe. tauschiiMAPK gene, a SOC1 orthologue and a pair of type-B two-component response regulators. Incorporating these exotic alleles into breeding programmes could serve as a pre-emptive strategy to produce high yielding wheat cultivars that are resilient to the effects of future climate uncertainty with no yield penalty under favourable conditions.
Actin remodelling controls proteasome homeostasis upon stress
Authors: Williams Thomas , Cacioppo Roberta , Agrotis Alexander , Black Ailsa , Zhou Houjiang , Rousseau Adrien 
Published: February 2022

AbstractWhen cells are stressed, bulk translation is often downregulated to reduce energy demands whilst stress-response proteins are simultaneously upregulated. 19S Regulatory Particle Assembly-Chaperones (RPACs) are selectively translated upon TORC1 inhibition to promote proteasome assembly and activity, maintaining cell viability. However, the molecular mechanism for such selective translational upregulation is unclear. Using yeast, we discover that remodelling of the actin cytoskeleton is important for RPAC translation following TORC1 inhibition. mRNA of the RPAC ADC17 travels along actin cables and is enriched at cortical actin patches under stress, dependent upon the early endocytic protein Ede1. ede1Δ cells failed to induce RPACs and proteasome assembly upon TORC1 inhibition. Conversely, artificially tethering ADC17 mRNA to cortical actin patches enhanced its translation upon stress. These findings suggest that actin dense structures such as cortical actin patches may serve as a translation platform for a subset of stress-induced mRNAs including regulators of proteasome homeostasis.
The Structure-Selective Endonucleases GEN1 and MUS81 are Functionally Complementary in Safeguarding the Genome of Proliferating B Lymphocytes
Authors: Fernandez Keith Conrad , Feeney Laura , Smolkin Ryan M. , Yen Wei-Feng , Matthews Allysia J. , Petrini John H. J. , Chaudhuri Jayanta 
Published: February 2022

ABSTRACTDuring the development of humoral immunity, activated B lymphocytes undergo vigorous proliferative, transcriptional, metabolic, and DNA remodeling activities; hence, their genomes are constantly exposed to an onslaught of genotoxic agents and processes. Recombination-dependent DNA transactions that preserve the integrity of the genome and of the DNA replication process generates Holliday junctions that must be eliminated for the accurate segregation of sister chromatids and faithful propagation of genomic material. To investigate the role of two Holliday junction resolvases, GEN1 and MUS81, in B cell biology, we established B-cell conditional knockout mouse models and found that targeted deletion of GEN1 and MUS81 in early B cell precursors halts their development and maturation while selective loss of the resolvases in mature B cells inhibits the generation of robust germinal centers. Upon activation, these double-null mature B lymphocytes fail to proliferate and survive while exhibiting transcriptional signatures of p53 signaling, apoptosis, and type I interferon response. Metaphase spreads of these resolvase-deficient cells showed severe and diverse chromosomal abnormalities, including a preponderance of chromosome breaks, consistent with a defect in resolving DNA recombination intermediates. These observations underscore the essential roles of GEN1 and MUS81 in safeguarding the genome to ensure the proper development and maintenance of B lymphocytes.
DBFE: Distribution-based feature extraction from copy number and structural variants in whole-genome data
Authors: Piernik Maciej , Brzezinski Dariusz , Sztromwasser Pawel , Pacewicz Klaudia , Majer-Burman Weronika , Gniot Michal , Sielski Dawid , Wozna Alicja , Zawadzki Pawel 
Published: February 2022

AbstractMotivationWhole-genome sequencing has revolutionized biosciences by providing tools for constructing complete DNA sequences of individuals. With entire genomes at hand, scientists can pinpoint DNA fragments responsible for different cancers and predict patient responses to cancer treatments. However, the sheer volume of whole-genome data makes it difficult to encode the characteristics of genomic variants as features for machine learning algorithms.ResultsWe present three feature extraction methods that facilitate classifier learning from distributions of genomic variants. The proposed approaches use binning, clustering, and kernel density estimation to produce features that discriminate between two groups of patients. Experiments on genomes of 219 ovarian, 61 lung, and 929 breast cancer patients show that the proposed approaches automatically identify genomic biomarkers associated with cancer subtypes and clinical response to oncological treatment. Finally, we show that the extracted features can be used alongside unsupervised learning methods to analyze genomic samples.AvailabilityThe source code of the presented algorithms and reproducible experimental scripts are available on Github at https://github.com/MNMdiagnostics/dbfeContactmaciej.piernik@cs.put.poznan.pl
Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve Split-Hand/Foot Malformation type 3
Authors: Cova Giulia , Glaser Juliane , Schöpflin Robert , Ali Salaheddine , Prada-Medina Cesar Augusto , Franke Martin , Falcone Rita , Federer Miriam , Ponzi Emanuela , Ficarella Romina , Novara Francesca , Wittler Lars , Timmermann Bernd , Gentile Mattia , Zuffardi Orsetta , Spielmann Malte , Mundlos Stefan 
Published: February 2022

ABSTRACTSplit-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. Yet, the disease patho-mechanism remains unsolved. Here we investigated the functional consequences of SHFM3-associated rearrangements on chromatin conformation and gene expression in vivo in transgenic mice. We show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. Re-engineering of a SHFM3-associated duplication and a newly reported inversion in mice resulted in restructuring of the chromatin architecture. This led to an ectopic activation of the Lbx1 and Btrc genes in the apical ectodermal ridge (AER) in an Fgf8-like pattern. Artificial repositioning of the AER-specific enhancers of Fgf8 was sufficient to induce misexpression of Lbx1 and Btrc. We provide evidence that the SHFM3 phenotype is the result of a combinatorial effect on gene misexpression and dosage in the developing limb. Our results reveal new insights into the molecular mechanism underlying SHFM3 and provide novel conceptual framework for how genomic rearrangements can cause gene misexpression and disease.
The guardian of the genome meets a viral master gene regulator at a biomolecular condensate
Authors: Borkosky Silvia Susana , Fassolari Marisol , Campos-León Karen , Rossi Andrés Hugo , Salgueiro Mariano , Pascuale Carla , Martínez Ramón Peralta , Gaston Kevin , de Prat Gay Gonzalo 
Published: February 2022

ABSTRACTAs guardian of the genome, p53 exerts its tumor suppressor activity by modulating the expression of several hundreds of genes and by interacting with a large number of proteins. However, p53 can also repress viral replication and it is targeted by a variety of viral proteins to allow viral replication to proceed. p53 can repress human papillomavirus replication by binding to the viral E2 master gene regulator. Here we show how full-length p53 can spontaneously form phase separated liquid-like droplets that evolve to amyloid-like aggregates in a time-dependent manner, highlighting the fact that homotypic condensation is on the path to aggregation as observed in several protein aggregopathies. The DNA binding domain of HPV E2 (E2C) triggers heterotypic liquid-liquid phase separation with p53 with a precise 1 p53 : 2 E2C stoichiometry at the onset for demixing, yielding large regular spherical droplets that increase in size with E2C concentration. Moreover, E2C is able to slowly reshape time-evolved p53 aggregates into regular heterotypic liquid droplets. Usingin situsub-cellular fractionation, we show that E2 and wild-type p53 co-localize to the nucleus with a grainy pattern, and E2 can re-localize p53 into chromatin associated foci, a function independent of the DNA binding capacity of p53. A small DNA duplex containing the specific binding site for p53 deforms and dissolves both homotypic and heterotypic condensates at a 1 p53 : 1 DNA stoichiometry, whereas a ∼1000 base pair DNA fragment instead reshaped the condensates into distinct amorphous condensates containing p53, E2C and DNA, reminiscent of what we observe bound to chromatin. We conclude that p53 is a scaffold for liquid-liquid phase separation in line with its structural and functional features, in particular as a hub that binds multiple cellular protein partners as well as nucleic acids. Moreover, the capacity of E2C to rescue p53 from the amyloid aggregation route impacts on p53-rescuing drugs cancers where p53 mutation leads to loss of function.