bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of Dhcr7 and Insig1/2 in cholesterol metabolism causes defects in bone formation and homeostasis through primary cilium formation
Authors: Suzuki Akiko , Ogata Kenichi , Yoshioka Hiroki , Shim Junbo , Wassif Christopher A. , Porter Forbes D. , Iwata Junichi 
Published: January 2020

AbstractHuman linkage studies suggest that craniofacial deformities result from either genetic mutations related to cholesterol metabolism or high-cholesterol maternal diets. However, little is known about the precise roles of intracellular cholesterol metabolism in the development of craniofacial bones, the majority of which are formed through intramembranous ossification. Here, we show that an altered cholesterol metabolic status results in abnormal osteogenesis through dysregulation of primary cilium formation during bone formation. We found that cholesterol metabolic aberrations, induced through disruption of eitherDhcr7(which encodes an enzyme involved in cholesterol synthesis) orInsig1andInsig2(which provide a negative feedback mechanism for cholesterol biosynthesis), result in osteoblast differentiation abnormalities. Notably, the primary cilia responsible for sensing extracellular cues were altered in number and length through dysregulated ciliary vesicle fusion inDhcr7andInsig1/2mutant osteoblasts. As a consequence, WNT/β-catenin and hedgehog signaling activities were altered through dysregulated primary cilium formation. Strikingly, the normalization of defective cholesterol metabolism by simvastatin, a drug used in the treatment of cholesterol metabolic aberrations, rescued the abnormalities in both ciliogenesis and osteogenesis in vitro and in vivo. Thus, our results indicate that proper intracellular cholesterol status is crucial for primary cilium formation during skull formation and homeostasis.
Inflammation-induced inhibition of chaperone-mediated autophagy maintains the immunosuppressive function of murine mesenchymal stromal cells
Authors: Zhang Jie , Huang Jiefang , Gu Yuting , Xue Mingxing , Qian Fengtao , Wang Bei , Yang Wanlin , Yu Hongshuang , Wang Qiwei , Guo Xin , Ding Xinyuan , Wang Jina , Jin Min , Zhang Yanyun 
Published: January 2020

AbstractMacroautophagy has been implicated in modulating the therapeutic function of mesenchymal stromal cells (MSCs). However, the biological function of chaperone-mediated autophagy (CMA) in MSCs remains elusive. Here, we found that CMA was inhibited in MSCs in response to the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). In addition, suppression of CMA by knocking down the CMA-related lysosomal receptor lysosomal-associated membrane protein 2 (LAMP-2A) in MSCs significantly enhanced the immunosuppressive effect of MSCs on T cell proliferation, and as expected, LAMP-2A overexpression in MSCs exerted the opposite effect on T cell proliferation. This effect of CMA on the immunosuppressive function of MSCs was attributed to its negative regulation of the expression of chemokine C-X-C motif ligand 10 (CXCL10), which recruits inflammatory cells, especially T cells, to MSCs, and inducible nitric oxide synthase (iNOS), which leads to the subsequent inhibition of T cell proliferation via nitric oxide (NO). Mechanistically, CMA inhibition dramatically promoted IFN-γ plus TNF-α-induced activation of NF-κB and STAT1, leading to the enhanced expression of CXCL10 and iNOS in MSCs. Furthermore, we found that IFN-γ plus TNF-α-induced AKT activation contributed to CMA inhibition in MSCs. More interestingly, CMA-deficient MSCs exhibited improved therapeutic efficacy in inflammatory liver injury. Taken together, our findings established CMA inhibition as a critical contributor to the immunosuppressive function of MSCs induced by inflammatory cytokines and highlighted a previously unknown function of CMA.
A wind-albedo-wind feedback driven by landscape evolution
Authors: Abell Jordan T. , Pullen Alex , Lebo Zachary J. , Kapp Paul , Gloege Lucas , Metcalf Andrew R. , Nie Junsheng , Winckler Gisela 
Published: January 2020

AbstractThe accurate characterization of near-surface winds is critical to our understanding of past and modern climate. Dust lofted by these winds has the potential to modify surface and atmospheric conditions as well as ocean biogeochemistry. Stony deserts, low dust emitting regions today, represent expansive areas where variations in surficial geology through time may drastically impact near-surface conditions. Here we use the Weather Research and Forecasting (WRF) model over the western Gobi Desert to demonstrate a previously undocumented process between wind-driven landscape evolution and boundary layer conditions. Our results show that altered surficial thermal properties through winnowing of fine-grained sediments and formation of low-albedo gravel-mantled surfaces leads to an increase in near-surface winds by up to 25%; paradoxically, wind erosion results in faster winds regionally. This wind-albedo-wind feedback also leads to an increase in the frequency of hours spent at higher wind speeds, which has implications for dust emission potential.
Mitochondrial TCA cycle metabolites control physiology and disease
Authors: Martínez-Reyes Inmaculada , Chandel Navdeep S. 
Published: January 2020

AbstractMitochondria are signaling organelles that regulate a wide variety of cellular functions and can dictate cell fate. Multiple mechanisms contribute to communicate mitochondrial fitness to the rest of the cell. Recent evidence confers a new role for TCA cycle intermediates, generally thought to be important for biosynthetic purposes, as signaling molecules with functions controlling chromatin modifications, DNA methylation, the hypoxic response, and immunity. This review summarizes the mechanisms by which the abundance of different TCA cycle metabolites controls cellular function and fate in different contexts. We will focus on how these metabolites mediated signaling can affect physiology and disease.
Catalytic processing in ruthenium-based polyoxometalate coacervate protocells
Authors: Gobbo Pierangelo , Tian Liangfei , Pavan Kumar B. V. V. S , Turvey Samuel , Cattelan Mattia , Patil Avinash J. , Carraro Mauro , Bonchio Marcella , Mann Stephen 
Published: January 2020

AbstractThe development of programmable microscale materials with cell-like functions, dynamics and collective behaviour is an important milestone in systems chemistry, soft matter bioengineering and synthetic protobiology. Here, polymer/nucleotide coacervate micro-droplets are reconfigured into membrane-bounded polyoxometalate coacervate vesicles (PCVs) in the presence of a bio-inspired Ru-based polyoxometalate catalyst to produce synzyme protocells (Ru4PCVs) with catalase-like activity. We exploit the synthetic protocells for the implementation of multi-compartmentalized cell-like models capable of collective synzyme-mediated buoyancy, parallel catalytic processing in individual horseradish peroxidase-containing Ru4PCVs, and chemical signalling in distributed or encapsulated multi-catalytic protocell communities. Our results highlight a new type of catalytic micro-compartment with multi-functional activity and provide a step towards the development of protocell reaction networks.
Ultrasensitive negative capacitance phototransistors
Authors: Tu Luqi , Cao Rongrong , Wang Xudong , Chen Yan , Wu Shuaiqin , Wang Fang , Wang Zhen , Shen Hong , Lin Tie , Zhou Peng , Meng Xiangjian , Hu Weida , Liu Qi , Wang Jianlu , Liu Ming , Chu Junhao 
Published: January 2020

AbstractSensitive photodetection is crucial for modern optoelectronic technology. Two-dimensional molybdenum disulfide (MoS2) with unique crystal structure, and extraordinary electrical and optical properties is a promising candidate for ultrasensitive photodetection. Previously reported methods to improve the performance of MoS2 photodetectors have focused on complex hybrid systems in which leakage paths and dark currents inevitably increase, thereby reducing the photodetectivity. Here, we report an ultrasensitive negative capacitance (NC) MoS2 phototransistor with a layer of ferroelectric hafnium zirconium oxide film in the gate dielectric stack. The prototype photodetectors demonstrate a hysteresis-free ultra-steep subthreshold slope of 17.64 mV/dec and ultrahigh photodetectivity of 4.75 × 1014 cm Hz1/2 W−1 at room temperature. The enhanced performance benefits from the combined action of the strong photogating effect induced by ferroelectric local electrostatic field and the voltage amplification based on ferroelectric NC effect. These results address the key challenges for MoS2 photodetectors and offer inspiration for the development of other optoelectronic devices.
Fluorinated hybrid solid-electrolyte-interphase for dendrite-free lithium deposition
Authors: Pathak Rajesh , Chen Ke , Gurung Ashim , Reza Khan Mamun , Bahrami Behzad , Pokharel Jyotshna , Baniya Abiral , He Wei , Wu Fan , Zhou Yue , Xu Kang , Qiao Qiquan 
Published: January 2020

AbstractLithium metal anodes have attracted extensive attention owing to their high theoretical specific capacity. However, the notorious reactivity of lithium prevents their practical applications, as evidenced by the undesired lithium dendrite growth and unstable solid electrolyte interphase formation. Here, we develop a facile, cost-effective and one-step approach to create an artificial lithium metal/electrolyte interphase by treating the lithium anode with a tin-containing electrolyte. As a result, an artificial solid electrolyte interphase composed of lithium fluoride, tin, and the tin-lithium alloy is formed, which not only ensures fast lithium-ion diffusion and suppresses lithium dendrite growth but also brings a synergistic effect of storing lithium via a reversible tin-lithium alloy formation and enabling lithium plating underneath it. With such an artificial solid electrolyte interphase, lithium symmetrical cells show outstanding plating/stripping cycles, and the full cell exhibits remarkably better cycling stability and capacity retention as well as capacity utilization at high rates compared to bare lithium.
An in vitro platform for engineering and harnessing modular polyketide synthases
Authors: Miyazawa Takeshi , Hirsch Melissa , Zhang Zhicheng , Keatinge-Clay Adrian T. 
Published: January 2020

AbstractTo harness the synthetic power of modular polyketide synthases (PKSs), many aspects of their biochemistry must be elucidated. A robust platform to study these megadalton assembly lines has not yet been described. Here, we in vitro reconstitute the venemycin PKS, a short assembly line that generates an aromatic product. Incubating its polypeptides, VemG and VemH, with 3,5-dihydroxybenzoic acid, ATP, malonate, coenzyme A, and the malonyl-CoA ligase MatB, venemycin production can be monitored by HPLC and NMR. Multi-milligram quantities of venemycin are isolable from dialysis-based reactors without chromatography, and the enzymes can be recycled. Assembly line engineering is performed using pikromycin modules, with synthases designed using the updated module boundaries outperforming those using the traditional module boundaries by over an order of magnitude. Using combinations of VemG, VemH, and their engineered derivatives, as well as the alternate starter unit 3-hydroxybenzoic acid, a combinatorial library of six polyketide products is readily accessed.
Integrative discovery of treatments for high-risk neuroblastoma
Authors: Almstedt Elin , Elgendy Ramy , Hekmati Neda , Rosén Emil , Wärn Caroline , Olsen Thale Kristin , Dyberg Cecilia , Doroszko Milena , Larsson Ida , Sundström Anders , Arsenian Henriksson Marie , Påhlman Sven , Bexell Daniel , Vanlandewijck Michael , Kogner Per , Jörnsten Rebecka , Krona Cecilia , Nelander Sven 
Published: January 2020

AbstractDespite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.
Absence of internal multidecadal and interdecadal oscillations in climate model simulations
Authors: Mann Michael E. , Steinman Byron A. , Miller Sonya K. 
Published: January 2020

AbstractFor several decades the existence of interdecadal and multidecadal internal climate oscillations has been asserted by numerous studies based on analyses of historical observations, paleoclimatic data and climate model simulations. Here we use a combination of observational data and state-of-the-art forced and control climate model simulations to demonstrate the absence of consistent evidence for decadal or longer-term internal oscillatory signals that are distinguishable from climatic noise. Only variability in the interannual range associated with the El Niño/Southern Oscillation is found to be distinguishable from the noise background. A distinct (40–50 year timescale) spectral peak that appears in global surface temperature observations appears to reflect the response of the climate system to both anthropogenic and natural forcing rather than any intrinsic internal oscillation. These findings have implications both for the validity of previous studies attributing certain long-term climate trends to internal low-frequency climate cycles and for the prospect of decadal climate predictability.
Fast and accurate sCMOS noise correction for fluorescence microscopy
Authors: Mandracchia Biagio , Hua Xuanwen , Guo Changliang , Son Jeonghwan , Urner Tara , Jia Shu 
Published: January 2020

AbstractThe rapid development of scientific CMOS (sCMOS) technology has greatly advanced optical microscopy for biomedical research with superior sensitivity, resolution, field-of-view, and frame rates. However, for sCMOS sensors, the parallel charge-voltage conversion and different responsivity at each pixel induces extra readout and pattern noise compared to charge-coupled devices (CCD) and electron-multiplying CCD (EM-CCD) sensors. This can produce artifacts, deteriorate imaging capability, and hinder quantification of fluorescent signals, thereby compromising strategies to reduce photo-damage to live samples. Here, we propose a content-adaptive algorithm for the automatic correction of sCMOS-related noise (ACsN) for fluorescence microscopy. ACsN combines camera physics and layered sparse filtering to significantly reduce the most relevant noise sources in a sCMOS sensor while preserving the fine details of the signal. The method improves the camera performance, enabling fast, low-light and quantitative optical microscopy with video-rate denoising for a broad range of imaging conditions and modalities.
Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5−CD44+ cells
Authors: Fu Dah-Jiun , Wang Lianghai , Chouairi Fouad K. , Rose Ian M. , Abetov Danysh A. , Miller Andrew D. , Yamulla Robert J. , Schimenti John C. , Flesken-Nikitin Andrea , Nikitin Alexander Yu. 
Published: January 2020

AbstractAreas of a junction between two types of epithelia are known to be cancer-prone in many organ systems. However, mechanisms for preferential malignant transformation at the junction areas remain insufficiently elucidated. Here we report that inactivation of tumor suppressor genes Trp53 and Rb1 in the gastric squamous-columnar junction (SCJ) epithelium results in preferential formation of metastatic poorly differentiated neoplasms, which are similar to human gastroesophageal carcinoma. Unlike transformation-resistant antral cells, SCJ cells contain a highly proliferative pool of immature Lgr5−CD44+ cells, which are prone to transformation in organoid assays, comprise early dysplastic lesions, and constitute up to 30% of all neoplastic cells. CD44 ligand osteopontin (OPN) is preferentially expressed in and promotes organoid formation ability and transformation of the SCJ glandular epithelium. OPN and CD44 overexpression correlate with the worst prognosis of human gastroesophageal carcinoma. Thus, detection and selective targeting of the active OPN-CD44 pathway may have direct clinical relevance.
A shared genetic basis of mimicry across swallowtail butterflies points to ancestral co-option of doublesex
Authors: Palmer Daniela H. , Kronforst Marcus R. 
Published: January 2020

AbstractUncovering whether convergent adaptations share a genetic basis is consequential for understanding the evolution of phenotypic diversity. This information can help us understand the extent to which shared ancestry or independent evolution shape adaptive phenotypes. In this study, we first ask whether the same genes underlie polymorphic mimicry in Papilio swallowtail butterflies. By comparing signatures of genetic variation between polymorphic and monomorphic species, we then investigate how ancestral variation, hybridization, and independent evolution contributed to wing pattern diversity in this group. We report that a single gene, doublesex (dsx), controls mimicry across multiple taxa, but with species-specific patterns of genetic differentiation and linkage disequilibrium. In contrast to widespread examples of phenotypic evolution driven by introgression, our analyses reveal distinct mimicry alleles. We conclude that mimicry evolution in this group was likely facilitated by ancestral polymorphism resulting from early co-option of dsx as a mimicry locus, and that evolutionary turnover of dsx alleles may underlie the wing pattern diversity of extant polymorphic and monomorphic lineages.
Simulated microgravity in the ring-sheared drop
Authors: McMackin Patrick M. , Griffin Shannon R. , Riley Frank P. , Gulati Shreyash , Debono Nicholas E. , Raghunandan Aditya , Lopez Juan M. , Hirsa Amir H. 
Published: January 2020

AbstractThe ring-sheared drop is a module for the International Space Station to study sheared fluid interfaces and their influence on amyloid fibril formation. A 2.54-cm diameter drop is constrained by a stationary sharp-edged ring at some latitude and sheared by the rotation of another ring in the other hemisphere. Shearing motion is conveyed primarily by the action of surface shear viscosity. Here, we simulate microgravity in the laboratory using a density-matched liquid surrounding the drop. Upon shearing, the drop’s deformation away from spherical is found to be a result of viscous and inertial forces balanced against the capillary force. We also present evidence that the deformation increases with increasing surface shear viscosity.
Accuracy of Vitalograph lung monitor as a screening test for COPD in primary care
Authors: Dickens A. P. , Fitzmaurice D. A. , Adab P. , Sitch A. , Riley R. D. , Enocson A. , Jordan R. E. 
Published: January 2020

AbstractMicrospirometry may be useful as the second stage of a screening pathway among patients reporting respiratory symptoms. We assessed sensitivity and specificity of the Vitalograph® lung monitor compared with post-bronchodilator confirmatory spirometry (ndd Easy on-PC) among primary care chronic obstructive pulmonary disease (COPD) patients within the Birmingham COPD cohort. We report a case–control analysis within 71 general practices in the UK. Eligible patients were aged ≥40 years who were either on a clinical COPD register or reported chronic respiratory symptoms on a questionnaire. Participants performed pre- and post-bronchodilator microspirometry, prior to confirmatory spirometry. Out of the 544 participants, COPD was confirmed in 337 according to post-bronchodilator confirmatory spirometry. Pre-bronchodilator, using the LLN as a cut-point, the lung monitor had a sensitivity of 50.5% (95% CI 45.0%, 55.9%) and a specificity of 99.0% (95% CI 96.6%, 99.9%) in our sample. Using a fixed ratio of FEV1/FEV6 < 0.7 to define obstruction in the lung monitor, sensitivity increased (58.8%; 95% CI 53.0, 63.8) while specificity was virtually identical (98.6%; 95% CI 95.8, 99.7). Within our sample, the optimal cut-point for the lung monitor was FEV1/FEV6 < 0.78, with sensitivity of 82.8% (95% CI 78.3%, 86.7%) and specificity of 85.0% (95% CI 79.4%, 89.6%). Test performance of the lung monitor was unaffected by bronchodilation. The lung monitor could be used in primary care without a bronchodilator using a simple ratio of FEV1/FEV6 as part of a screening pathway for COPD among patients reporting respiratory symptoms.
Depth-to-bedrock map of China at a spatial resolution of 100 meters
Authors: Yan Fapeng , Shangguan Wei , Zhang Jing , Hu Bifeng 
Published: January 2020

AbstractDepth to bedrock influences or controls many of the Earth’s physical and chemical processes. It plays important roles in soil science, geology, hydrology, land surface processes, civil engineering, and other related fields. However, information about depth to bedrock in China is very deficient, and there is no independent map of depth to bedrock in China currently. This paper describes the materials and methods to produce high-resolution (100 m) depth-to-bedrock maps of China. For different research and application needs, two sets of data are provided for users. One is the prediction by the ensemble of the random forests and gradient boosting tree models, and the other is the prediction and the uncertainty of prediction based on quantile regression forests model. In comparison with depth-to-bedrock maps of China extracted from previous global predictions, our predictions showed higher accuracy and more spatial details. These data sets can provide more accurate information for Earth system research compared with previous depth-to-bedrock maps.
A homogeneous bioluminescent immunoassay to probe cellular signaling pathway regulation
Authors: Hwang Byounghoon , Engel Laurie , Goueli Said A. , Zegzouti Hicham 
Published: January 2020

AbstractMonitoring cellular signaling events can help better understand cell behavior in health and disease. Traditional immunoassays to study proteins involved in signaling can be tedious, require multiple steps, and are not easily adaptable to high throughput screening (HTS). Here, we describe a new immunoassay approach based on bioluminescent enzyme complementation. This immunoassay takes less than two hours to complete in a homogeneous “Add and Read” format and was successfully used to monitor multiple signaling pathways’ activation through specific nodes of phosphorylation (e.g pIκBα, pAKT, and pSTAT3). We also tested deactivation of these pathways with small and large molecule inhibitors and obtained the expected pharmacology. This approach does not require cell engineering. Therefore, the phosphorylation of an endogenous substrate is detected in any cell type. Our results demonstrate that this technology can be broadly adapted to streamline the analysis of signaling pathways of interest or the identification of pathway specific inhibitors.