bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative Proteomic Analysis of Posttranslational Modification in The Inflammatory Response
Authors: Ji Feiyang , Zhou Menghao , Zhu Huihui , Jiang Zhengyi , Li Qirui , Ouyang Xiaoxi , Lv Yiming , Zhang Sainan , Wu Tian , Li Lanjuan 
Published: July 2020

AbstractThe posttranslational modification (PTM) of proteins, particularly acetylation, phosphorylation and ubiquitination, plays a critical role in the host innate immune response. PTMs’ dynamic changes and the crosstalk among them are complicated. To build a comprehensive dynamic network of inflammation related proteins, we integrated data from the whole cell proteome (WCP), acetylome, phosphoproteome and ubiquitinome of human and mouse macrophages. Our datasets of acetylation, phosphorylation and ubiquitination sites helped identify PTM crosstalk within and across proteins involved in the inflammatory response. Stimulation of macrophages by lipopolysaccharide (LPS) resulted in both degradative and non-degradative ubiquitination. Moreover, this study contributes to the interpretation of the roles of known inflammatory molecules and the discovery of novel inflammatory proteins.
Discovery of membrane-permeating cyclic peptides via mRNA display
Authors: Bowen John , Schloop Allison E. , Reeves Gregory T. , Menegatti Stefano , Rao Balaji M. 
Published: July 2020

AbstractSmall synthetic peptides capable of crossing biological membranes represent valuable tools in cell biology and drug delivery. While several cell-penetrating peptides (CPPs) of natural or synthetic origin have been reported, no peptide is currently known to cross both cytoplasmic and outer embryonic membranes. Here we describe a method to engineer membrane-permeating cyclic peptides (MPPs) with broad permeation activity by screening mRNA display libraries of cyclic peptides against embryos at different developmental stages. The proposed method was demonstrated by identifying peptides capable of permeatingDrosophila melanogaster(fruit fly) embryos and mammalian cells. The selected peptide cyclo[Glut-MRKRHASRRE-K*] showed a strong permeation activity of embryos exposed to minimal permeabilization pretreatment, as well as human embryonic stem cells and a murine fibroblast cell line. Notably, in both embryos and mammalian cells, the cyclic peptide outperformed its linear counterpart and the control MPPs. Confocal microscopy and single cell flow cytometry analysis were utilized to assess the degree of permeation both qualitatively and quantitatively. These MPPs have potential application in studying and non-disruptively controlling intracellular or intraembryonic processes.
Imaging biomarkers for motor outcome after stroke – should we include information from beyond the primary motor system?
Authors: Sperber Christoph , Rennig Johannes , Karnath Hans-Otto 
Published: July 2020

AbstractHemiparesis is a common consequence of stroke to the primary motor system. Previous studies suggested that damage to additional brain areas might play a causal role in the occurrence and severity of hemiparesis and its recovery. Knowledge of these regions might be applied in the creation of imaging biomarkers for motor outcome prediction if lesion information from such areas carries predictive value. We assessed acute and chronic paresis of the upper limb in 102 patients with unilateral stroke. In a first experiment, the neural correlates of acute and chronic upper limb paresis were mapped by lesion behaviour mapping. Following the same approach, a lesion biomarker of corticospinal tract (CST) damage was mapped. This analysis served as an artificial control condition as the biomarker, by definition, is only causally related to damage of the CST. Mapping acute or chronic upper limb paresis implicated areas outside of the primary motor system. Likewise, mapping the CST lesion biomarker implicated several areas outside of the CST with high correspondence to areas associated with upper limb paresis. Damage to areas outside of the primary motor system thus might, to some degree, not play a causal role in hemiparesis. In a second experiment, we showed that lesion information from these areas outside of the primary motor system can be used to predict motor outcome. This was even the case for the CST lesion biomarker. Although the only causal source underlying the CST lesion biomarker was damage to the CST, lesion information that mainly included non-CST regions was able to predict the biomarker (non-significantly) better than information taken from only the CST itself. These findings suggest that simple theory-based biomarkers or qualitative rules to infer post-stroke outcome from imaging data might perform sub-optimally, as they do not consider the complexity of lesion data. Instead, high-dimensional models with data-driven feature selection strategies might be required.
Global patterns of aegyptism without arbovirus
Authors: Olson Mark F. , Juarez José G. , Kraemer Moritz U. G. , Messina Jane P. , Hamer Gabriel L. 
Published: July 2020

ABSTRACTThe world’s most important mosquito vector of viruses, Aedes aegypti, is found around the world in tropical, subtropical and even some temperate locations. While climate change may limit populations of Ae. aegypti in some regions, increasing temperatures will likely expand its territory thus increasing risk of human exposure to arboviruses in places like Europe, Northern Australia and North America, among many others. Most studies of Ae. aegypti biology and virus transmission focus on locations with high endemicity or severe outbreaks of human amplified urban arboviruses, such as dengue, Zika, and chikungunya viruses, but rarely on areas at the margins of endemicity. Our objective in this study is to explore global patterns in the environmental suitability for Ae. aegypti and dengue virus to reveal deviations in the probability of the vector and human disease occurring. We developed a map showing one end of the gradient being higher suitability of Ae. aegypti with low suitability of dengue and the other end of the spectrum being equal and higher environmental suitability for both Ae. aegypti and dengue. The regions of the world with Ae. aegypti environmental suitability and no endemic dengue transmission exhibits a phenomenon we term ‘aegyptism without arbovirus’. We then tested what environmental and socioeconomic variables influence this deviation map revealing a significant association with population density, suggesting that locations with lower population density were more likely to have a higher probability of aegyptism without arbovirus. Characterizing regions of the world with established populations of Ae. aegypti but little to no autochthonous transmission of human-amplified arboviruses is an important step in understanding and achieving aegyptism without arbovirus.
MHC class IIa haplotypes derived by high throughput SNP screening in an isolated sheep population
Authors: Dicks K.L. , Pemberton J.M. , Ballingall K.T. , Johnston S.E. 
Published: July 2020

ABSTRACTInvestigating the current evolutionary processes acting on a highly polymorphic gene region, such as the major histocompatibility complex (MHC), requires extensive population data for both genotypes and phenotypes. The MHC consists of several tightly linked loci with both allelic and gene content variation, making it challenging to genotype. Eight class IIa haplotypes have previously been identified in the Soay sheep (Ovis aries) of St. Kilda using Sanger sequencing and cloning, but no single locus is representative of all haplotypes. Here, we exploit the closed nature of the island population of Soay sheep and its limited haplotypic variation to identify a panel of SNPs that enable imputation of MHC haplotypes. We compared MHC class IIa haplotypes determined by Sanger sequence-based genotyping of 135 individuals to their SNP profiles generated using the Ovine Infinium HD BeadChip. A panel of 11 SNPs could reliably determine MHC diplotypes, and two additional SNPs within theDQA1gene enabled detection of a recombinant haplotype affecting only the SNPs downstream of the expressed genes. The panel of 13 SNPs was genotyped in 5951 Soay sheep, of which 5349 passed quality control. Using the Soay sheep pedigree, we were able to trace the origin and inheritance of the recombinant SNP haplotype. This SNP-based method has enabled the rapid generation of locus-specific MHC genotypes for large numbers of Soay sheep. This volume of high-quality genotypes in a well-characterized population of free-living sheep will be valuable for investigating the mechanisms maintaining diversity at the MHC.
Regulation of immune receptor kinases plasma membrane nanoscale landscape by a plant peptide hormone and its receptors
Authors: Gronnier Julien , Franck Christina M. , Stegmann Martin , DeFalco Thomas A. , Abarca Alicia , Von Arx Michelle , Dünser Kai , Lin Wenwei , Yang Zhenbiao , Kleine-Vehn Jürgen , Ringli Christoph , Zipfel Cyril 
Published: July 2020

ABSTRACTSpatial partitioning is a propensity of biological systems orchestrating cell activities in space and time. The dynamic regulation of plasma membrane nano-environments has recently emerged as a key fundamental aspect of plant signaling, but the molecular components governing it are still mostly unclear. The receptor kinase FERONIA (FER) controls complex formation of the immune receptor kinase FLAGELLIN SENSING 2 (FLS2) with its co-receptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1), and this function is inhibited by the FER ligand RAPID ALKALANIZATION FACTOR 23 (RALF23). Here, we show that FER regulates the plasma membrane nanoscale organization of FLS2 and BAK1. Our study demonstrates that akin to FER, leucine-rich repeat (LRR) extensin (LRXs) proteins contribute to RALF23 responsiveness, regulate BAK1 nanoscale organization and immune signaling. Furthermore, RALF23 perception leads to rapid modulation of FLS2 and BAK1 nanoscale organization and its inhibitory activity on immune signaling relies on FER kinase activity. Our results suggest that perception of RALF peptides by FER and LRXs actively modulates the plasma membrane nanoscale landscape to regulate cell surface signaling by other receptor kinases.
Chemogenetic silencing of hippocampus and amygdala reveals a double dissociation in periadolescent obesogenic diet-induced memory alterations
Authors: Naneix Fabien , Bakoyiannis Ioannis , Santoyo-Zedillo Marianela , Bosch-Bouju Clémentine , Pacheco-Lopez Gustavo , Coutureau Etienne , Ferreira Guillaume ,   OBETEEN Consortium
Published: July 2020

1ABSTRACTIn addition to numerous metabolic comorbidities, obesity is associated with several adverse neurobiological outcomes, especially learning and memory alterations. Obesity prevalence is rising dramatically in youth and is persisting in adulthood. This is especially worrying since adolescence is a crucial period for the maturation of certain brain regions playing a central role in memory processes such as the hippocampus and the amygdala. We previously showed that periadolescent exposure to obesogenic high-fat diet (HFD) had opposite effects on hippocampus- and amygdala-dependent memory, impairing the former and enhancing the latter. However, the causal role of these two brain regions in periadolescent HFD-induced memory alterations remains unclear. Here, we first showed that periadolescent HFD induced long-term, but not short-term, object recognition memory deficits, specifically when rats were exposed to a novel context. Using chemogenetic approaches to inhibit targeted brain regions, we then demonstrated that recognition memory deficits are dependent on the activity of the ventral hippocampus, but not the basolateral amygdala. On the contrary, the HFD-induced enhancement of conditioned odor aversion requires specifically amygdala activity. Taken together, these findings suggest that HFD consumption throughout adolescence impairs long-term object recognition memory through the overactivation of the ventral hippocampus during memory acquisition. Moreover, these results further highlight the bidirectional effects of adolescent HFD on hippocampal and amygdala functions.
Identifying functional metabolic shifts in heart failure with the integration of omics data and a cardiomyocyte-specific, genome-scale model
Authors: Dougherty Bonnie V. , Rawls Kristopher D. , Kolling Glynis L. , Vinnakota Kalyan C. , Wallqvist Anders , Papin Jason A. 
Published: July 2020

SummaryThe heart is a metabolic omnivore, known to consume many different carbon substrates in order to maintain function. In diseased states, the heart’s metabolism can shift between different carbon substrates; however, there is some disagreement in the field as to the metabolic shifts seen in end-stage heart failure and whether all heart failure converges to a common metabolic phenotype. Here, we present a new, validated cardiomyocyte-specific GEnome-scale metabolic Network REconstruction (GENRE),iCardio, and use the model to identify common shifts in metabolic functions across heart failure omics datasets. We demonstrate the utility ofiCardioin interpreting heart failure gene expression data by identifying Tasks Inferred from Differential Expression (TIDEs) which represent metabolic functions associated with changes in gene expression. We identify decreased NO and Neu5Ac synthesis as common metabolic markers of heart failure across datasets. Further, we highlight the differences in metabolic functions seen across studies, further highlighting the complexity of heart failure. The methods presented for constructing a tissue-specific model and identifying TIDEs can be extended to multiple tissue and diseases of interest.
ThePIF1-MIR408-PlantacyaninRepression Cascade Regulates Light Dependent Seed Germination
Authors: Jiang Anlong , Guo Zhonglong , Pan Jiawei , Zhuang Yan , Zuo Daqing , Hao Chen , Gao Zhaoxu , Xin Peiyong , Chu Jinfang , Zhong Shangwei , Li Lei 
Published: July 2020

ABSTRACTLight-sensing seed germination is a vital process for the seed plants. A decisive event in light-induced germination is degradation of the central repressor PHYTOCHROME INTERACTING FACTOR1 (PIF1). It is also known that the balance between gibberellic acid (GA) and abscisic acid (ABA) critically controls germination. But the cellular mechanisms linking PIF1 turnover to hormonal rebalancing remain elusive. Here, employing far-red light-inducedArabidopsisseed germination as the experimental system, we identified Plantacyanin (PLC) as an inhibitor of germination, which is a storage vacuole-associated blue copper protein highly expressed in mature seed and rapidly silenced during germination. Molecular analyses showed that PIF1 directly binds to theMIR408promoter and represses miR408 accumulation, which in turn post-transcriptionally modulatesPLCabundance, thus forming thePIF1-MIR408-PLCrepression cascade for translating PIF1 turnover to PLC turnover during early germination. Genetic analysis, RNA-sequencing, and hormone quantification revealed thatPLCis necessary and sufficient to maintain thePIF1-mediated seed transcriptome and the low-GA-high-ABA state. Furthermore, we found that PLC domain organization and regulation by miR408 are conserved features in seed plants. These results unraveled a cellular mechanism whereby PIF1-relayed external light signals are converted through PLC-based copper mobilization into internal hormonal profiles for controlling seed germination.
Spatiotemporal single-cell profiling of gastrointestinal GVHD reveals invasive and resident memory T cell states
Authors: Tkachev Victor , Kaminski James , Potter E. Lake , Furlan Scott N. , Yu Alison , Hunt Daniel J. , McGuckin Connor , Zheng Hengqi , Colonna Lucrezia , Gerdemann Ulrike , Carlson Judith , Hoffman Michelle , Olvera Joe , English Chris , Baldessari Audrey , Panoskaltsis-Mortari Angela , Watkins Benjamin , Qayed Muna , Suessmuth Yvonne , Betz Kayla , Bratrude Brandi , Langston Amelia , Horan John , Ordovas-Montanes Jose , Shalek Alex K. , Blazar Bruce R. , Roederer Mario , Kean Leslie S. 
Published: July 2020

ABSTRACTOne of the central challenges in the field of allo-immunity is deciphering the mechanisms driving T cells to infiltrate and subsequently occupy target organs to cause disease. The act of CD8-dominated T cell infiltration is critical to acute graft-versus-host disease (aGVHD), wherein donor T cells become activated, tissue-infiltrating and highly cytotoxic, causing wide-spread tissue damage after allogeneic hematopoietic stem cell transplant (allo-HCT). However, in human and non-human primate studies, deconvolving the transcriptional programs of newly recruited relative to resident memory T cells in the gastrointestinal (GI) tract has remained a challenge. In this study, we combined the novel technique of Serial Intravascular Staining (SIVS) with single-cell RNA-Seq (scRNA-seq) to enable detailed dissection of the tightly connected processes by which T cells first infiltrate tissues and then establish a pathogenic tissue residency program after allo-HCT in non-human primates. Our results have enabled the creation of a spatiotemporal map of the transcriptional drivers of CD8 T cell infiltration into the primary aGVHD target-organ, the GI tract. We identify the large and small intestines as the only two sites demonstrating allo-specific, rather than lymphdepletion-driven T cell infiltration. The donor CD8 T cells that infiltrate the GI tract demonstrate a highly activated, cytotoxic phenotype while simultaneously rapidly developing canonical tissue-resident memory (TRM) protein expression and transcriptional signatures, driven by IL-15/IL-21 signaling. Moreover, by combining SIVS and transcriptomic analysis, we have been able to work backwards from this pathogenic TRMprograming, and, for the first time, identify a cluster of genes directly associated with tissue invasiveness, prominently including specific chemokines and adhesion molecules and their receptors, as well as a central cytoskeletal transcriptional node. The clinical relevance of this new tissue invasion signature was validated by its ability to discriminate the CD8 T cell transcriptome of patients with GI aGVHD. These results provide new insights into the mechanisms controlling tissue infiltration and pathogenic CD8 TRMtranscriptional programing, uncovering critical transitions in allo-immune tissue invasion and destruction.One sentence summaryFlow cytometric and transcriptomic analysis reveals coordinated tissue-infiltration and tissue-residency programs driving gastrointestinal aGVHD.
Impact of cell-type and context-dependent regulatory variants on human immune traits
Authors: Mu Zepeng , Wei Wei , Fair Benjamin , Miao Jinlin , Zhu Ping , Li Yang I 
Published: July 2020

AbstractThe effects of trait-associated variants are often studied in a single relevant cell-type or context. However, for many complex traits, multiple cell-types are involved. This applies particularly to immune-related traits, for which many immune cell-types and contexts play a role. Here, we studied the impact of immune gene regulatory variants on complex traits to better understand genetic risk mediated through immune cell-types. We identified 26,271 expression quantitative trait loci (QTLs) and 23,121 splicing QTLs in 18 immune cell-types, and analyzed their overlap with trait-associated loci from 72 genome-wide association studies (GWAS). We showed that effects on RNA expression and splicing in immune cells colocalize with an average of 40.4% and 27.7% GWAS loci for immune-related and non-immune traits, respectively. Notably, we found that a large number of loci (mean: 14%) colocalize with splicing QTLs but not expression QTLs. The 60% GWAS loci without colocalization harbor genes that have lower expression levels, are less tolerant to loss-of-function mutations, and more enhancerrich than genes at colocalized loci. To further investigate the 60% GWAS loci not explained by our regulatory QTLs, we collected H3K27ac CUT&Tag data from rheumatoid arthritis (RA) and healthy controls. We found several unexplained GWAS hits lying within regions with higher H3K27ac activity in RA patients. We also observed that enrichment of RA GWAS heritability is greater in H3K27ac regions in immune cell-types from RA patients compared to healthy controls. Our study paves the way for future QTL studies to elucidate the mechanisms of as yet unexplained GWAS loci.
Raman imaging analysis of microvesicular and macrovesicular lipid droplets in non-alcoholic fatty liver disease
Authors: Minamikawa Takeo , Ichimura-Shimizu Mayuko , Takanari Hiroki , Morimoto Yuki , Shiomi Ryosuke , Tanioka Hiroki , Hase Eiji , Yasui Takeshi , Tsuneyama Koichi 
Published: July 2020

AbstractPredominant evidence of non-alcoholic fatty liver disease (NAFLD) is the accumulation of excess lipids in the liver. A small group with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH). However, there is a lack of investigation of the accumulated lipids with spatial and molecular information. Raman microscopy has the potential to characterize molecular species and structures of lipids based on molecular vibration and can achieve high spatial resolution at the organelle level. We aim to demonstrate the feasibility of Raman microscopy for the investigation of NAFLD based on the molecular features of accumulated lipids. By applying the Raman microscopy to the liver of the NASH model mice, we succeeded in visualizing the distribution of lipid droplets (LDs) in hepatocytes. The detailed analysis of Raman spectra revealed the difference of molecular structural features of the LDs, such as the degree of saturation of lipids in the LDs. We also found that the inhomogeneous distribution of cholesterol in the LDs depending on the histology of lipid accumulation. We visualized and characterized the lipids of NASH model mice by Raman microscopy at organelle level. Our findings demonstrated that the Raman imaging analysis was feasible to characterize the NAFLD in terms of the molecular species and structures of lipids.
Magnetic Temporal Interference For Noninvasive, High-resolution, and Localized Deep Brain Stimulation: Concept Validation
Authors: Zaeimbashi Mohsen , Khalifa Adam , Dong Cunzheng , Wei Yuyi , Cash Sydney , Sun Nian 
Published: July 2020

AbstractNon-invasive deep brain stimulation has been a major challenge in the field of neuroscience and brain stimulation in the past three decades. Current brain stimulation technologies suffer from such hurdles as the inability to do deep brain stimulation, poor spatial resolution, and invasiveness. Transcranial magnetic stimulation (TMS) technique, for instance, cannot target brain regions deeper than ∼2cm and has a poor spatial resolution, impacting a large area of the peripheral region and leading to various side effects. Implantable electrodes, even though effective for deep brain stimulation, are invasive and carry various drawbacks related to the surgery and site infection. In this paper, we propose a new concept that relies on temporal interference of two high- frequency magnetic fields generated by two electromagnetic coils. The neural system does not respond to each of these high-frequency magnetic fields alone because of the intrinsic low-pass filtering properties of the neural membrane. The peripheral areas of the brain are impacted only by the high-frequency magnetic fields that cannot stimulate the nerves, while the deep brain area where the two fields interfere experiences a magnetic field that contains a low-frequency envelope and therefore the nerves can be stimulated. This technique can noninvasively focus a magnetic or electric beam at any depth inside the brain with a high resolution, without impacting the peripheral regions.