bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPRY4 is responsible for pathogenesis of adolescent idiopathic scoliosis by contributing to osteogenic differentiation and melatonin response of bone marrow-derived mesenchymal stem cells
Authors: Li Jing , Li Na , Chen Yunfei , Hui Shangyi , Fan Junfen , Ye Buqing , Fan Zusen , Zhang Jianguo , Zhao Robert Chunhua , Zhuang Qianyu 
Published: October 2019

AbstractAdolescent idiopathic scoliosis (AIS) is a complex, three-dimensional deformity of the spine that commonly occurs in pubescent girls. Decreased osteogenic differentiation and aberrant melatonin signalling have been demonstrated in mesenchymal stem cells (MSCs) from AIS patients and are implicated in the pathogenesis of AIS. However, the molecular mechanisms underlying these abnormal cellular features remain largely unknown. Our previous work comparing gene expression profiles between MSCs from AIS patients and healthy controls identified 1027 differentially expressed genes. In the present study, we focused on one of the most downregulated genes, SPRY4, in the MAPK signalling pathway and examined its role in osteogenic differentiation. We found that SPRY4 is markedly downregulated in AIS MSCs. Knockdown of SPRY4 impaired differentiation of healthy MSCs to osteoblasts, while SPRY4 overexpression in AIS MSCs enhanced osteogenic differentiation. Furthermore, melatonin treatment boosted osteogenic differentiation, whereas SPRY4 ablation ablated the promotional effects of melatonin. Moreover, SPRY4 was upregulated by melatonin exposure and contributed to osteogenic differentiation and melatonin response in a MEK-ERK1/2 dependent manner. Thus, loss of SPRY4 in bone marrow derived-MSCs results in reduced osteogenic differentiation, and these defects are further aggravated under the influence of melatonin. Our findings provide new insights for understanding the role of melatonin in AIS aetiology and highlight the importance of MSCs in AIS pathogenesis.
Enhanced hexosamine metabolism drives metabolic and signaling networks involving hyaluronan production and O-GlcNAcylation to exacerbate breast cancer
Authors: Chokchaitaweesuk Chatchadawalai , Kobayashi Takashi , Izumikawa Tomomi , Itano Naoki 
Published: October 2019

AbstractThe hexosamine biosynthetic pathway (HBP) metabolically regulates dynamic cellular events by linking nutrient availability to numerous signaling networks. Significant alterations in the HBP are often associated with cancer pathogenesis. In this study, we investigated the molecular events underlying cancer pathogenesis associated with enhanced HBP flux. Multidimensional analysis of microarray datasets demonstrated up-regulation of genes encoding HBP enzymes in clinical breast cancers and revealed that co-expression of hyaluronan synthase 2 (HAS2) and glutamine:fructose-6-phosphate amidotransferase (GFAT), a rate-limiting enzyme of the HBP, was strongly correlated with a poor prognosis in advanced cancer patients. Consistently with the clinical data, comparative analyses of distinct breast cancer mouse models demonstrated enhancement of the HBP gene expression in primary carcinoma cells, with elevation of Has2 expression and hyaluronan production in aggressive breast cancer cells. The silencing of GFAT reduced CD44high/CD24low cancer stem cell (CSC)-like subpopulations, aldehyde dehydrogenase-positive cell populations, and mammosphere size, which were further diminished by gene targeting of Has2. Has2 gene disruption reduced the in vivo growth of aggressive cancer cells and attenuated pro-tumorigenic Akt/GSK3β/β-catenin signaling and cisplatin resistance. Overall protein O-GlcNAcylation was also elevated in association with HBP enhancement in aggressive cancer cells, and the modification exhibited overlapping but distinct roles from the hyaluronan signal in the regulation of CSC-like features. The current data therefore demonstrate that enhanced hexosamine metabolism drives pro-tumorigenic signaling pathways involving hyaluronan and O-GlcNAcylation in aggressive breast cancer.
Autophagy regulates the therapeutic potential of adipose-derived stem cells in LPS-induced pulmonary microvascular barrier damage
Authors: Li Chichi , Pan Jingye , Ye Lechi , Xu Honglei , Wang Beibei , Xu Hanyan , Xu Lingna , Hou Tongtong , Zhang Dan 
Published: October 2019

AbstractAdipose-derived stem cells (ADSCs) have been shown to be beneficial in some pulmonary diseases, and the paracrine effect is the major mechanism underlying ADSC-based therapy. Autophagy plays a crucial role in maintaining stem cell homeostasis and survival. However, the role of autophagy in mediating ADSC paracrine effects has not been thoroughly elucidated. We examined whether ADSCs participate in lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial cell (PMVEC) barrier damage in a paracrine manner and illuminated the role of autophagy in regulating ADSC paracrine effects. PMVECs and ADSCs with or without autophagy inhibition were cocultured without intercellular contact, and the microvascular barrier function was assessed after LPS treatment. ADSC paracrine function was evaluated by detecting essential growth factors for endothelial cells. For in vivo experiments, ADSCs with or without autophagy inhibition were transplanted into LPS-induced lung-injury mice, and lung injury was assessed. ADSCs significantly alleviated LPS-induced microvascular barrier injury. In addition, ADSC paracrine levels of VEGF, FGF, and EGF were induced by LPS treatment, especially in the coculture condition. Inhibiting autophagy weakened the paracrine function and the protective effects of ADSCs on microvascular barrier injury. Moreover, ADSC transplantation alleviated LPS-induced lung injury, and inhibiting autophagy markedly weakened the therapeutic effect of ADSCs on lung injury. Together, these findings show that ADSC paracrine effects play a vital protective role in LPS-induced pulmonary microvascular barrier injury. Autophagy is a positive mediating factor in the paracrine process. These results are helpful for illuminating the role and mechanism of ADSC paracrine effects and developing effective therapies in acute lung injury.
A multiscale signalling network map of innate immune response in cancer reveals cell heterogeneity signatures
Authors: Kondratova Maria , Czerwinska Urszula , Sompairac Nicolas , Amigorena Sebastian D. , Soumelis Vassili , Barillot Emmanuel , Zinovyev Andrei , Kuperstein Inna 
Published: October 2019

AbstractThe lack of integrated resources depicting the complexity of the innate immune response in cancer represents a bottleneck for high-throughput data interpretation. To address this challenge, we perform a systematic manual literature mining of molecular mechanisms governing the innate immune response in cancer and represent it as a signalling network map. The cell-type specific signalling maps of macrophages, dendritic cells, myeloid-derived suppressor cells and natural killers are constructed and integrated into a comprehensive meta map of the innate immune response in cancer. The meta-map contains 1466 chemical species as nodes connected by 1084 biochemical reactions, and it is supported by information from 820 articles. The resource helps to interpret single cell RNA-Seq data from macrophages and natural killer cells in metastatic melanoma that reveal different anti- or pro-tumor sub-populations within each cell type. Here, we report a new open source analytic platform that supports data visualisation and interpretation of tumour microenvironment activity in cancer.
GTPase-activating protein Rasal1 associates with ZAP-70 of the TCR and negatively regulates T-cell tumor immunity
Authors: Thaker Youg Raj , Raab Monika , Strebhardt Klaus , Rudd Christopher E. 
Published: October 2019

AbstractImmunotherapy involving checkpoint blockades of inhibitory co-receptors is effective in combating cancer. Despite this, the full range of mediators that inhibit T-cell activation and influence anti-tumor immunity is unclear. Here, we identify the GTPase-activating protein (GAP) Rasal1 as a novel TCR-ZAP-70 binding protein that negatively regulates T-cell activation and tumor immunity. Rasal1 inhibits via two pathways, the binding and inhibition of the kinase domain of ZAP-70, and GAP inhibition of the p21ras-ERK pathway. It is expressed in activated CD4 + and CD8 + T-cells, and inhibits CD4 + T-cell responses to antigenic peptides presented by dendritic cells as well as CD4 + T-cell responses to peptide antigens in vivo. Furthermore, siRNA reduction of Rasal1 expression in T-cells shrinks B16 melanoma and EL-4 lymphoma tumors, concurrent with an increase in CD8 + tumor-infiltrating T-cells expressing granzyme B and interferon γ-1. Our findings identify ZAP-70-associated Rasal1 as a new negative regulator of T-cell activation and tumor immunity.
The greenhouse gas impacts of converting food production in England and Wales to organic methods
Authors: Smith Laurence G. , Kirk Guy J. D. , Jones Philip J. , Williams Adrian G. 
Published: October 2019

AbstractAgriculture is a major contributor to global greenhouse gas (GHG) emissions and must feature in efforts to reduce emissions. Organic farming might contribute to this through decreased use of farm inputs and increased soil carbon sequestration, but it might also exacerbate emissions through greater food production elsewhere to make up for lower organic yields. To date there has been no rigorous assessment of this potential at national scales. Here we assess the consequences for net GHG emissions of a 100% shift to organic food production in England and Wales using life-cycle assessment. We predict major shortfalls in production of most agricultural products against a conventional baseline. Direct GHG emissions are reduced with organic farming, but when increased overseas land use to compensate for shortfalls in domestic supply are factored in, net emissions are greater. Enhanced soil carbon sequestration could offset only a small part of the higher overseas emissions.
Principles of meiotic chromosome assembly revealed in S. cerevisiae
Authors: Schalbetter Stephanie A. , Fudenberg Geoffrey , Baxter Jonathan , Pollard Katherine S. , Neale Matthew J. 
Published: October 2019

AbstractDuring meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we useSaccharomyces cerevisiaeto explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent inS. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process.
Self-assembling peptides imaged by correlated liquid cell transmission electron microscopy and MALDI-imaging mass spectrometry
Authors: Touve Mollie A. , Carlini Andrea S. , Gianneschi Nathan C. 
Published: October 2019

AbstractWe describe the observation of stimuli-induced peptide-based nanoscale assemblies by liquid cell transmission electron microscopy (LCTEM). LCTEM offers the opportunity to directly image nanoscale materials in liquid. Despite broad interest in characterizing biological phenomena, electron beam-induced damage remains a significant problem. Concurrently, methods for verifying chemical structure during or following an LCTEM experiment have been few, with key examples limited to electron diffraction or elemental analysis of crystalline materials; this strategy is not translatable to biopolymers observed in nature. In this proof-of-concept study, oligomeric peptides are biologically or chemically stimulated within the liquid cell in a TEM to assemble into nanostructures. The resulting materials are analyzed by MALDI-imaging mass spectrometry (MALDI-IMS) to verify their identity. This approach confirms whether higher-order assemblies observed by LCTEM consist of intact peptides, verifying that observations made during the in situ experiment are because of those same peptides and not aberrant electron beam damage effects.
Cellular and synaptic phenotypes lead to disrupted information processing in Fmr1-KO mouse layer 4 barrel cortex
Authors: Domanski Aleksander P. F. , Booker Sam A. , Wyllie David J. A. , Isaac John T. R. , Kind Peter C. 
Published: October 2019

AbstractSensory hypersensitivity is a common and debilitating feature of neurodevelopmental disorders such as Fragile X Syndrome (FXS). How developmental changes in neuronal function culminate in network dysfunction that underlies sensory hypersensitivities is unknown. By systematically studying cellular and synaptic properties of layer 4 neurons combined with cellular and network simulations, we explored how the array of phenotypes in Fmr1-knockout (KO) mice produce circuit pathology during development. We show that many of the cellular and synaptic pathologies in Fmr1-KO mice are antagonistic, mitigating circuit dysfunction, and hence may be compensatory to the primary pathology. Overall, the layer 4 network in the Fmr1-KO exhibits significant alterations in spike output in response to thalamocortical input and distorted sensory encoding. This developmental loss of layer 4 sensory encoding precision would contribute to subsequent developmental alterations in layer 4-to-layer 2/3 connectivity and plasticity observed in Fmr1-KO mice, and circuit dysfunction underlying sensory hypersensitivity.
CRISPR-mediated gene silencing reveals involvement of the archaeal S-layer in cell division and virus infection
Authors: Zink Isabelle Anna , Pfeifer Kevin , Wimmer Erika , Sleytr Uwe B. , Schuster Bernhard , Schleper Christa 
Published: October 2019

AbstractThe S-layer is a proteinaceous surface lattice found in the cell envelope of bacteria and archaea. In most archaea, a glycosylated S-layer constitutes the sole cell wall and there is evidence that it contributes to cell shape maintenance and stress resilience. Here we use a gene-knockdown technology based on an endogenous CRISPR type III complex to gradually silence slaB, which encodes the S-layer membrane anchor in the hyperthermophilic archaeon Sulfolobus solfataricus. Silenced cells exhibit a reduced or peeled-off S-layer lattice, cell shape alterations and decreased surface glycosylation. These cells barely propagate but increase in diameter and DNA content, indicating impaired cell division; their phenotypes can be rescued through genetic complementation. Furthermore, S-layer depleted cells are less susceptible to infection with the virus SSV1. Our study highlights the usefulness of the CRISPR type III system for gene silencing in archaea, and supports that an intact S-layer is important for cell division and virus susceptibility.
Modeling and simulation of complex dynamic musculoskeletal architectures
Authors: Zhang Xiaotian , Chan Fan Kiat , Parthasarathy Tejaswin , Gazzola Mattia 
Published: October 2019

AbstractNatural creatures, from fish and cephalopods to snakes and birds, combine neural control, sensory feedback and compliant mechanics to effectively operate across dynamic, uncertain environments. In order to facilitate the understanding of the biophysical mechanisms at play and to streamline their potential use in engineering applications, we present here a versatile numerical approach to the simulation of musculoskeletal architectures. It relies on the assembly of heterogenous, active and passive Cosserat rods into dynamic structures that model bones, tendons, ligaments, fibers and muscle connectivity. We demonstrate its utility in a range of problems involving biological and soft robotic scenarios across scales and environments: from the engineering of millimeter-long bio-hybrid robots to the synthesis and reconstruction of complex musculoskeletal systems. The versatility of this methodology offers a framework to aid forward and inverse bioengineering designs as well as fundamental discovery in the functioning of living organisms.
A mutualistic interaction between Streptomyces bacteria, strawberry plants and pollinating bees
Authors: Kim Da-Ran , Cho Gyeongjun , Jeon Chang-Wook , Weller David M. , Thomashow Linda S. , Paulitz Timothy C. , Kwak Youn-Sig 
Published: October 2019

AbstractMicrobes can establish mutualistic interactions with plants and insects. Here we track the movement of an endophytic strain of Streptomyces bacteria throughout a managed strawberry ecosystem. We show that a Streptomyces isolate found in the rhizosphere and on flowers protects both the plant and pollinating honeybees from pathogens (phytopathogenic fungus Botrytis cinerea and pathogenic bacteria, respectively). The pollinators can transfer the Streptomyces bacteria among flowers and plants, and Streptomyces can move into the plant vascular bundle from the flowers and from the rhizosphere. Our results present a tripartite mutualism between Streptomyces, plant and pollinator partners.
Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms
Authors: Fusco Salvatore , Spinelli Matteo , Cocco Sara , Ripoli Cristian , Mastrodonato Alessia , Natale Francesca , Rinaudo Marco , Livrizzi Giulia , Grassi Claudio 
Published: October 2019

AbstractMetabolic diseases harm brain health and cognitive functions, but whether maternal metabolic unbalance may affect brain plasticity of next generations is still unclear. Here, we demonstrate that maternal high fat diet (HFD)-dependent insulin resistance multigenerationally impairs synaptic plasticity, learning and memory. HFD downregulates BDNF and insulin signaling in maternal tissues and epigenetically inhibits BDNF expression in both germline and hippocampus of progeny. Notably, exposure of the HFD offspring to novel enriched environment restores Bdnf epigenetic activation in the male germline and counteracts the transmission of cognitive impairment to the next generations. BDNF administration to HFD-fed mothers or preserved insulin sensitivity in HFD-fed p66Shc KO mice also prevents the intergenerational transmission of brain damage to the progeny. Collectively, our data suggest that maternal diet multigenerationally impacts on descendants’ brain health via gametic mechanisms susceptible to lifestyle.
A secreted microRNA disrupts autophagy in distinct tissues of Caenorhabditis elegans upon ageing
Authors: Zhou Yifei , Wang Xueqing , Song Mengjiao , He Zhidong , Cui Guizhong , Peng Guangdun , Dieterich Christoph , Antebi Adam , Jing Naihe , Shen Yidong 
Published: October 2019

AbstractMacroautophagy, a key player in protein quality control, is proposed to be systematically impaired in distinct tissues and causes coordinated disruption of protein homeostasis and ageing throughout the body. Although tissue-specific changes in autophagy and ageing have been extensively explored, the mechanism underlying the inter-tissue regulation of autophagy with ageing is poorly understood. Here, we show that a secreted microRNA, mir-83/miR-29, controls the age-related decrease in macroautophagy across tissues in Caenorhabditis elegans. Upregulated in the intestine by hsf-1/HSF1 with age, mir-83 is transported across tissues potentially via extracellular vesicles and disrupts macroautophagy by suppressing CUP-5/MCOLN, a vital autophagy regulator, autonomously in the intestine as well as non-autonomously in body wall muscle. Mutating mir-83 thereby enhances macroautophagy in different tissues, promoting protein homeostasis and longevity. These findings thus identify a microRNA-based mechanism to coordinate the decreasing macroautophagy in various tissues with age.
Giant anisotropic thermal expansion actuated by thermodynamically assisted reorientation of imidazoliums in a single crystal
Authors: Yao Zi-Shuo , Guan Hanxi , Shiota Yoshihito , He Chun-Ting , Wang Xiao-Lei , Wu Shu-Qi , Zheng Xiaoyan , Su Sheng-Qun , Yoshizawa Kazunari , Kong Xueqian , Sato Osamu , Tao Jun 
Published: October 2019

AbstractMaterials demonstrating unusual large positive and negative thermal expansion are fascinating for their potential applications as high-precision microscale actuators and thermal expansion compensators for normal solids. However, manipulating molecular motion to execute huge thermal expansion of materials remains a formidable challenge. Here, we report a single-crystal Cu(II) complex exhibiting giant thermal expansion actuated by collective reorientation of imidazoliums. The circular molecular cations, which are rotationally disordered at a high temperature and statically ordered at a low temperature, demonstrate significant reorientation in the molecular planes. Such atypical molecular motion, revealed by variable-temperature single crystal X-ray diffraction and solid-state NMR analyses, drives an exceptionally large positive thermal expansion and a negative thermal expansion in a perpendicular direction of the crystal. The consequent large shape change (~10%) of bulk material, with remarkable durability, suggests that this complex is a strong candidate as a microscale thermal actuating material.
Tracking vegetation phenology across diverse biomes using Version 2.0 of the PhenoCam Dataset
Authors: Seyednasrollah Bijan , Young Adam M. , Hufkens Koen , Milliman Tom , Friedl Mark A. , Frolking Steve , Richardson Andrew D. 
Published: October 2019

AbstractMonitoring vegetation phenology is critical for quantifying climate change impacts on ecosystems. We present an extensive dataset of 1783 site-years of phenological data derived from PhenoCam network imagery from 393 digital cameras, situated from tropics to tundra across a wide range of plant functional types, biomes, and climates. Most cameras are located in North America. Every half hour, cameras upload images to the PhenoCam server. Images are displayed in near-real time and provisional data products, including timeseries of the Green Chromatic Coordinate (Gcc), are made publicly available through the project web page (https://phenocam.sr.unh.edu/webcam/gallery/). Processing is conducted separately for each plant functional type in the camera field of view. The PhenoCam Dataset v2.0, described here, has been fully processed and curated, including outlier detection and expert inspection, to ensure high quality data. This dataset can be used to validate satellite data products, to evaluate predictions of land surface models, to interpret the seasonality of ecosystem-scale CO2 and H2O flux data, and to study climate change impacts on the terrestrial biosphere.