bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Functional Annotation of Long Intergenic Non-coding RNAs in the Brassicaceae
Authors: Palos Kyle , Dittrich Anna C. Nelson , Yu Li’ang , Brock Jordan R. , Wu Larry , Sokolowska Ewelina , Skirycz Aleksandra , Hsu Polly , Lyons Eric , Beilstein Mark A. , Nelson Andrew D. L. 
Published: September 2021

AbstractLong intergenic noncoding RNAs (lincRNAs) are a large yet enigmatic class of eukaryotic transcripts with critical biological functions. Despite the wealth of RNA-seq data available, lincRNA identification lags in the plant lineage. In addition, there is a need for a harmonized identification and annotation effort to enable cross-species functional and genomic comparisons. In this study we processed >24 Tbp of RNA-seq data from >16,000 experiments to identify ~130,000 lincRNAs in four Brassicaceae: Arabidopsis thaliana, Camelina sativa, Brassica rapa, and Eutrema salsugineum. We used Nanopore RNA-seq, transcriptome-wide structural information, peptide data, and epigenomic data to characterize these lincRNAs and identify functional motifs. We then used comparative genomic and transcriptomic approaches to highlight lincRNAs in our dataset with sequence or transcriptional evolutionary conservation, including lincRNAs transcribed adjacent to orthologous genes that display little sequence similarity and likely function as transcriptional regulators. Finally, we used guilt-by-association techniques to further classify these lincRNAs according to putative function. LincRNAs with Brassicaceae-conserved putative miRNA binding motifs, short ORFs, and whose expression is modulated by abiotic stress are a few of the annotations that will prioritize and guide future functional analyses.
Integrative Analysis of Spatial Transcriptome with Single-cell Transcriptome and Single-cell Epigenome in Mouse Lungs after Immunization
Authors: Xu Zhongli , Wang Xinjun , Fan Li , Wang Fujing , Wang Jiebiao , Chen Wei , Chen Kong 
Published: September 2021

ABSTRACTImmunological memory is key to productive adaptive immunity. An unbiased, high throughput gene expression profiling of tissue-resident memory T cells at their precise anatomical locations within the lung is fundamental to understanding lung immunity, but such spatial information has yet to be characterized. In this study, using a well-established Klebsiella pneumoniae infection model, we performed an integrative analysis of spatial transcriptome with single-cell RNA-seq and single-cell ATAC-seq on lung cells from mice after immunization using the 10x Genomics Chromium and Visium platform. We employed several deconvolution algorithms and established an optimized deconvolution pipeline to accurately decipher specific cell-type composition by anatomic location. We identified and located 12 major cell types by scRNA-seq and spatial transcriptomic analysis. Integrating scATAC-seq data from the same cells processed in parallel with scRNA-seq, we found epigenomic profiles provide more robust cell type identification, especially for lineage-specific T helper cells. When combining all three data modalities, we observed a dynamic change in the location of T helper cells as well as their corresponding chemokines for chemotaxis. Furthermore, cell-cell communication analysis of spatial transcriptome provided evidence of lineage-specific T helper cells receiving designated cytokine signaling. In summary, our first-in-class study demonstrated the power of multi-omics analysis to uncover intrinsic spatial- and cell-type-dependent molecular mechanisms of lung immunity. Our data provides a rich research resource of single cell multi-omics data as a reference for understanding spatial dynamics of lung immunization.
A ppGpp-mediated brake on photosynthesis is required for acclimation to nitrogen limitation in Arabidopsis
Authors: Romand Shanna , Abdelkefi Hela , Lecampion Cecile , Belaroussi Mohamed , Dussenne Melanie , Ksas Brigitte , Citerne Sylvie , Caius José , D’Alessandro Stefano , Fakhfakh Hatem , Caffarri Stefano , Havaux Michel , Field Ben 
Published: September 2021

AbstractGuanosine pentaphosphate and tetraphosphate (together referred to as ppGpp) are hyperphosphorylated nucleotides found in bacteria and the chloroplasts of plants and algae. In plants and algae artificial ppGpp accumulation can inhibit chloroplast gene expression, and influence photosynthesis, nutrient remobilisation, growth, and immunity. However, it is so far unknown whether ppGpp is required for abiotic stress acclimation in plants. Here, we demonstrate that ppGpp biosynthesis is necessary for acclimation to nitrogen starvation in Arabidopsis. We show that ppGpp is required for remodeling the photosynthetic electron transport chain to downregulate photosynthetic activity and for protection against oxidative stress. Furthermore, we demonstrate that ppGpp is required for coupling chloroplastic and nuclear gene expression during nitrogen starvation. Altogether, our work indicates that ppGpp is a pivotal regulator of chloroplast activity for stress acclimation in plants.
Shedding light on biosilica morphogenesis by comparative analysis of the silica-associated proteomes from three diatom species
Authors: Skeffington Alastair W. , Gentzel Marc , Ohara Andre , Milentyev Alexander , Heintze Christoph , Böttcher Lorenz , Görlich Stefan , Shevchenko Andrej , Poulsen Nicole , Kröger Nils 
Published: September 2021

SummaryMorphogenesis of the intricate patterns of diatom silica cell walls is a protein-guided process, yet to date only very few such silica morphogenetic proteins have been identified. Therefore, it is unknown whether all diatoms share conserved proteins of a basal silica forming machinery, and whether unique proteins are responsible for the morphogenesis of species specific silica patterns.To answer these questions, we extracted proteins from the silica of three diatom species (Thalassiosira pseudonana, Thalassiosira oceanica and Cyclotella cryptica) by complete demineralization of the cell walls. LC-MS/MS analysis of the extracts identified 92 proteins that we name ‘Soluble Silicome Proteins’ (SSPs).Surprisingly, no SSPs are common to all three species, and most SSPs showed very low similarity to one another in sequence alignments. In depth bioinformatics analyses revealed that SSPs can be grouped into distinct classes bases on short unconventional sequence motifs whose functions are yet unknown. The results from in vivo localization of selected SSPs indicates that proteins, which lack sequence homology but share unconventional sequence motifs may exert similar functions in the morphogenesis of the diatom silica cell wall.
Chromomycin A5 induces bonafide immunogenic cell death in metastatic melanoma
Authors: Florêncio Katharine G. D. , Edson Evelline A. , Pinto Francisco C. L. , Pessoa Otília D. L. , Machado-Neto João Agostinho , Wilke Diego V. 
Published: September 2021

AbstractSome first-line cytotoxic chemotherapics, e.g. doxorubicin, paclitaxel and oxaliplatin, induce activation of the immune system through immunogenic cell death (ICD). Tumor cells undergoing ICD function as a vaccine, releasing damage-associated molecular patterns (DAMPs), which act as adjuvants, and neoantigens of the tumor are recognized as antigens. ICD induction is rare, however it yields better and long-lasting antitumor responses to chemotherapy. Advanced metastatic melanoma (AMM) is incurable for more than half of patients. The discovery of ICD inducers against AMM is an interesting drug discovery strategy with high translational potential. Here we evaluated ICD induction of four highly cytotoxic chromomycins A (CA5-8). B16-F10, a metastatic melanoma cell line, treated with CA5-8 and doxorubicin exhibited ICD features such as autophagy and apoptosis, externalization of calreticulin, and releasing of HMGB1. However, CA5-treated cells had the best profile, also inducing ATP release, ERp57 externalization, phosphorylation of eIF2α and altering expression of transcription of genes related to autophagy, endoplasmic reticulum stress, and apoptosis. Bonafide ICD induction by CA5 was confirmed by a C57BL/6 mice vaccination assay with CA5-treated cells. These findings support a high potential of CA5 as an anticancer candidate against AMM.
Willingness to wait covaries with endogenous variation in cortisol
Authors: Lukinova Evgeniya , Erlich Jeffrey C. 
Published: September 2021

AbstractStress is a normal part of our everyday lives. It alerts us to changes in our environment working as an early warning system. However, when stress is prolonged, it can become harmful. The deleterious effects of stress on brain function are well established: chronic stress significantly impairs cognitive function reducing our ability to solve problems and to regulate behavior and, therefore, may lead to more challenges that can further exacerbate stress. An important class of decisions that may be made under stress includes those between rewards delivered immediately vs. those delivered in the future. Not considering or devaluing future outcomes (delay discounting) can result in adverse outcomes such as not buying health insurance, gambling or drug use. To date, however, little is known about how chronic stress influences economic decisions that differ in the time of outcome delivery. A handful of studies suggest that increased stress may lead to more impulsive choices in subjects of average socioeconomic status and stress levels. Here, we addressed this gap by using a longitudinal design to determine whether chronic stress measures (via questionnaires, saliva and hair samples) are associated with the economic choices under different time scales within subject (N = 34). We found that the degree to which people think it is worth waiting, i.e. individual’s discount factor, over seconds, but not over days, varied reliably with endogenous stress. These results are imperative to studying stress in a variety of contexts: e.g., the variation in consumer’s impulse purchases could be attributed to the variation in individual stress responses to the environment, even in healthy adults.
Spatio-temporal analysis of remote sensing images provides early warning signals of forest mortality
Authors: Alibakhshi Sara 
Published: September 2021

AbstractEcosystems are under unprecedented pressures, reflected in rapid changes in the regime of disturbances that may cause negative impacts on them. This highlights the importance of characterizing the state of an ecosystem and its response to disturbances, which is known as a notoriously difficult task. The state-of-the-art knowledge has been tested rarely in real ecosystems for a number of reasons such as mismatches between the time scale of ecosystem processes and data accessibility as well as weaknesses in the performance of available methods. This study aims to use remotely sensed spatio-temporal data to identify early warning signals of forest mortality using satellite images. For this purpose, I propose a new approach that measures local spatial autocorrelation (using local Moran’s I and local Geary’s c method) at each time, which proved to produce robust results in multiple different study sites examined in this article. This new approach successfully generates early warning signals from time series of local spatial autocorrelation values in unhealthy study sites 2 years prior to forest mortality occurrence. Furthermore, I develop a new R package, called “stew”, that enables users to explore spatio-temporal analysis of ecosystem state changes. This work corroborates the suggestion that spatio-temporal indicators have the potential to diagnose early warning signals to identify upcoming climate-induced forest mortality, up to two years before its occurrence.
Dynamics of p53 DNA binding sites contributes to functional selectivity of p53-driven gene expression
Authors: Safieh Jessy , Chazan Ariel , Vyas Pratik , Saleem Hanna , Danin-Poleg Yael , Ron Dina , Haran Tali E. 
Published: September 2021

AbstractThe tumor suppressor protein p53 is situated in the midst of a complex network that is activated in response to cellular stress. An unresolved question is how p53 activates its myriad target genes in response to the severity of the stress signal and consequently coordinates the functional outcome in a timely manner. We have previously shown that DNA torsional flexibility distinguishes among p53 response elements (REs). Here we calculated the flexibility of over 200 p53 REs. By connecting functional pathways of p53-dependent genes to the calculated flexibility of their REs, we show that genes belonging to pathways activated rapidly upon stress (e.g., cell-cycle arrest, energy metabolism and innate immunity) contain REs that are significantly more flexible relative to REs of genes involved in pathways that need to be more strictly regulated or are activated later in the response to stress (e.g., intrinsic apoptosis and p53 negative regulation). The global structural properties of several p53 REs belonging to the different pathways were experimentally validated. Additionally, reporter gene expression driven by flexible p53 REs occurred at lower p53 levels and with faster rates than expression from rigid REs. Moreover, analysis of published endogenous mRNA levels of p53 target genes as a function of the flexibility of their REs support our hypothesis. Overall, we demonstrate that DNA flexibility of p53 REs contributes significantly to the timely expression of p53 target genes and thereby plays an important role in cell-faith decisions in the p53 circuity.
Novel biochemical, structural and systems insights into inflammatory signaling revealed by contextual interaction proteomics
Authors: Ciuffa Rodolfo , Uliana Federico , Mehnert Martin , Marulli Cathy , Satanowski Ari , Rodilla Ramírez Pilar Natalia , Meier Pascal , Ori Alessandro , Gstaiger Matthias , Aebersold Ruedi 
Published: September 2021

AbstractProtein-protein interactions (PPI) represent the main mode of the proteome organization in the cell. In the last decade, several large-scale representations of PPI networks have captured generic aspects of the functional organization of network components, but mostly lack the context of cellular states. However, the generation of contextual representations of PPI networks is essential for structural and systems-level modeling of biological processes and remains an unsolved challenge. In this study we describe an integrated experimental/computational strategy to achieve a contextualized modeling of PPI. This strategy defines the composition, stoichiometry, spatio-temporal organization and cellular requirements for the formation of target assemblies. We used this approach to generate an integrated model of the formation principles and architecture of a large signalosome, the TNF-receptor signaling complex (TNF-RSC). Overall, we show that the integration of systems- and structure-level information provides a generic, largely unexplored link between the modular proteome and cellular function.Significance StatementIn this work, we propose a critical shift in the way we analyze, and think the study of, protein-protein interactions (PPI), and present an experimental and computational framework to model them in the cellular context. We applied this framework to the signalosome tumor necrosis factor receptor signaling complex (TNF-RSC), and generated an integrated model of its formation and architecture that provides new insights and resolved controversies regarding its organization and regulation. To achieve a contextual modelling of PPIs, we first optimized and developed, and then combined, approaches to map the composition of a target complex, its absolute stoichiometry, its spatial organization and assembly/disassembly dynamics, its temporal dependence on signaling, and its reliance on cellular resources.
Ribosomal RNA 2’-O-methylations regulate translation by impacting ribosome dynamics
Authors: Khoshnevis Sohail , Dreggors-Walker R. Elizabeth , Marchand Virginie , Motorin Yuri , Ghalei Homa 
Published: September 2021

AbstractProtein synthesis by ribosomes is critically important for gene expression in all cells. The ribosomal RNAs (rRNAs) are marked by numerous chemical modifications. An abundant group of rRNA modifications, present in all domains of life, is 2’-O-methylation guided by box C/D small nucleolar RNAs (snoRNAs) which are part of small ribonucleoprotein complexes (snoRNPs). Although 2’-O-methylations are required for proper production of ribosomes, the mechanisms by which these modifications contribute to translation have remained elusive. Here, we show that a change in box C/D snoRNP biogenesis in actively growing yeast cells results in the production of hypo 2’-O-methylated ribosomes with distinct translational properties. Using RiboMeth-Seq for the quantitative analysis of 2’-O methylations, we identify site-specific perturbations of the rRNA 2’-O-methylation pattern and uncover sites that are not required for ribosome production under normal conditions. Characterization of the hypo 2’-O-methylated ribosomes reveals significant translational fidelity defects including frameshifting and near-cognate start codon selection. Using rRNA structural probing, we show that hypo 2’-O-methylation affects the inherent dynamics of the ribosomal subunits and impacts the binding of translation factor eIF1 thereby causing translational defects. Our data reveal an unforeseen spectrum of 2’-O-methylation heterogeneity in yeast rRNA and suggest a significant role for rRNA 2’-O-methylation in regulating cellular translation by controlling ribosome dynamics and ligand binding.
Progenitor cell integration into a barrier epithelium during adult organ turnover
Authors: Moreno-Roman Paola , Su Yu-Han , Galenza Anthony , Acosta-Alvarez Lehi , Debec Alain , Guichet Antoine , Knapp Jon-Michael , Kizilyaprak Caroline , Humbel Bruno M. , Kolotuev Irina , O’Brien Lucy Erin 
Published: September 2021

ABSTRACTBarrier epithelial organs face the constant challenge of sealing the interior body from the external environment while simultaneously replacing the cells that contact this environment. These replacement cells—the progeny of basal stem cells—are born without apical, barrier-forming structures such as a protective, lumen-facing membrane and occluding junctions. How stem cell progeny acquire these structures to become part of the barrier is unknown. Here we use Focused Ion Beam-Scanning Electron Microscopy (FIB-SEM), Correlative Light-Electron Microscopy (CLEM), and volumetric imaging of live and fixed organs to investigate progenitor integration in the intestinal epithelium of adult Drosophila. We find that stem cell daughters gestate their future lumenal-apical membrane beneath a transient, basal niche formed by an umbrella-shaped occluding junction that shelters the growing cell and adheres it to mature neighbor cells. The umbrella junction both targets formation of a deep, microvilli-lined, apical invagination and closes it off from the contents of the gut lumen. When the growing cell is sufficiently mature, the umbrella junction retracts to expose this Pre-Assembled Apical Compartment (PAAC) to the gut lumen, thus incorporating the new cell into the intestinal barrier. When we block umbrella junctions, stem cell daughters grow and attempt to differentiate but fail to integrate; when we block cell growth, no umbrella junctions form and daughters arrest in early differentiation. Thus, stem cell progeny build new barrier structures in the shelter of a transient niche, where they are protected from lumenal insults until they are prepared to withstand them. By coordinating this dynamic junctional niche with progenitor cell differentiation, a physiologically active epithelial organ incorporates new cells while upholding integrity of its barrier.
The master energy homeostasis regulator PGC-1α couples transcriptional co-activation and mRNA nuclear export
Authors: Mihaylov Simeon R. , Castelli Lydia M. , Lin Ya-Hui , Gül Aytac , Soni Nikita , Hastings Christopher , Flynn Helen R. , Dickman Mark J. , Snijders Ambrosius P. , Bandmann Oliver , Mortiboys Heather , Ultanir Sila K. , Hautbergue Guillaume M. 
Published: September 2021

AbstractPGC-1α plays a central role in maintaining the mitochondrial and energy metabolism homeostasis, linking external stimuli to the transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and a putative RNA recognition motif, however potential RNA-processing role(s) have remained elusive for the past 20 years. Here, we show that the RS domain of human PGC-1α directly interacts with RNA and the nuclear RNA export factor NXF1. Inducible depletion of endogenous PGC-1α and expression of RNAi-resistant RS-deleted PGC-1α further demonstrate that the RNA-binding activity is required for nuclear export of co-activated transcripts and mitochondrial homeostasis. Moreover, a quantitative proteomics approach confirmed PGC-1α-dependent RNA transport and mitochondrial-related functions, identifying also novel mRNA nuclear export targets in age-related telomere maintenance. Discovering a novel function for a major cellular homeostasis regulator provides new directions to further elucidate the roles of PGC-1α in gene expression, metabolic disorders, ageing and neurodegenerative diseases.
Mitochondrial UPR negatively regulates wounding-induced innate immune response in C. elegans epidermis
Authors: Zhao Jianzhi , Fu Hongying , Zhou Hengda , Ren Xuecong , Wang Yuanyuan , Xu Suhong 
Published: September 2021

AbstractTissue damage elicits a rapid innate immune response that is essential for efficient wound healing and survival of metazoans. It is well known that p38 MAPK kinase, TGF-β, and hemidesmosome signaling pathways have been involved in wounding-induced innate immunity in C. elegans. Here, we find that loss of function of ATFS-1 increased innate immune response while an elevated level of mitochondrial unfolded protein response (mitoUPR) inhibits the innate immune response upon epidermal wounding. Epidermal wounding triggers the nucleus export of ATFS-1 and inhibits themitoUPR in C. elegans epidermis. Moreover, genetic analysis suggests that ATFS-1 functions upstream of the p38 MAP kinase, TGF-β and DAF-16 signaling pathways in regulating AMPs induction. Thus, our results suggest that the mitoUPR function as an intracellular signal required to fine-tune innate immune response after tissue damage.Highlights—ATFS-1 inhibits the wounding-induced innate immune response in C. elegans—mitoUPR inhibits wounding-induced innate immune response—Epidermal wounding induces downregulation of ATFS-1 in the epidermis—mitoUPR acts upstream of p38MAPK and TGF-β pathways to regulate innate immunity