bluuebunny/crossref_metadata_2025_split huggingface dataset:
RANK promotes colorectal cancer migration and invasion by activating the Ca2+-calcineurin/NFATC1-ACP5 axis
Authors: Liang Qian , Wang Yun , Lu Yingsi , Zhu Qingqing , Xie Wenlin , Tang Nannan , Huang Lifen , An Tailai , Zhang Di , Yan Anqi , Liu Shaoyu , Ye Liping , Zhu Chengming 
Published: April 2021

AbstractThe tumor necrosis factor (TNF) receptor superfamily member 11a (TNFRSF11a, also known as RANK) was demonstrated to play an important role in tumor metastasis. However, the specific function of RANK in colorectal cancer (CRC) metastasis and the underlying mechanism are unknown. In this study, we found that RANK expression was markedly upregulated in CRC tissues compared with that in matched noncancerous tissues. Increased RANK expression correlated positively with metastasis, higher TNM stage, and worse prognosis in patients with CRC. Overexpression of RANK promoted CRC cell metastasis in vitro and in vivo, while knockdown of RANK decreased cell migration and invasion. Mechanistically, RANK overexpression significantly upregulated the expression of tartrate-resistant acid phosphatase 5 (TRAP/ACP5) in CRC cells. Silencing of ACP5 in RANK-overexpressing CRC cells attenuated RANK-induced migration and invasion, whereas overexpression of ACP5 increased the migration and invasion of RANK-silencing cells. The ACP5 expression was transcriptionally regulated by calcineurin/nuclear factor of activated T cells c1 (NFATC1) axis. The inhibition of calcineurin/NFATC1 significantly decreased ACP5 expression, and attenuated RANK-induced cell migration and invasion. Furthermore, RANK induced phospholipase C-gamma (PLCγ)-mediated inositol-1,4,5-trisphosphate receptor (IP3R) axis and stromal interaction molecule 1 (STIM1) to evoke calcium (Ca2+) oscillation. The RANK-mediated intracellular Ca2+ mobilization stimulated calcineurin to dephosphorylate NFATC1 and induce NFATC1 nuclear translocation. Both blockage of PLCγ-IP3R axis and STIM1 rescued RANK-induced NFATC1 nuclear translocation, ACP5 expression, and cell metastasis. Our study revealed the functional expression of RANK in human CRC cells and demonstrated that RANK induced the Ca2+-calcineurin/NFATC1-ACP5 axis in the regulation of CRC metastasis, that might be amenable to therapeutic targeting.
Growth hormone induces mitotic catastrophe of glomerular podocytes and contributes to proteinuria
Authors: Nishad Rajkishor , Mukhi Dhanunjay , Singh Ashish Kumar , Motrapu Manga , Chintala Kumaraswami , Tammineni Prasad , Pasupulati Anil K. 
Published: April 2021

AbstractGlomerular podocytes are integral members of the glomerular filtration barrier in the kidney and are crucial for glomerular permselectivity. These highly differentiated cells are vulnerable to an array of noxious stimuli that prevail in several glomerular diseases. Elevated circulating growth hormone (GH) levels are associated with podocyte injury and proteinuria in diabetes. However, the precise mechanism(s) by which excess GH elicits podocytopathy remains to be elucidated. Previous studies have shown that podocytes express GH receptor (GHR) and induce Notch signaling when exposed to GH. In the present study, we demonstrated that GH induces TGF-β1 signaling and provokes cell cycle reentry of otherwise quiescent podocytes. Though differentiated podocytes reenter the cell cycle in response to GH and TGF-β1, they cannot accomplish cytokinesis, despite karyokinesis. Owing to this aberrant cell cycle event, GH- or TGF-β1-treated cells remain binucleated and undergo mitotic catastrophe. Importantly, inhibition of JAK2, TGFBR1 (TGF-β receptor 1), or Notch prevented cell cycle reentry of podocytes and protected them from mitotic catastrophe associated with cell death. Inhibition of Notch activation prevents GH-dependent podocyte injury and proteinuria. Similarly, attenuation of GHR expression abated Notch activation in podocytes. Kidney biopsy sections from patients with diabetic nephropathy (DN) show activation of Notch signaling and binucleated podocytes. These data indicate that excess GH induced TGF-β1-dependent Notch1 signaling contributes to the mitotic catastrophe of podocytes. This study highlights the role of aberrant GH signaling in podocytopathy and the potential application of TGF-β1 or Notch inhibitors, as a therapeutic agent for DN.
Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity
Authors: Sogkas Georgios , Atschekzei Faranaz , Adriawan Ignatius Ryan , Dubrowinskaja Natalia , Witte Torsten , Schmidt Reinhold Ernst 
Published: April 2021

AbstractIn addition to susceptibility to infections, conventional primary immunodeficiency disorders (PIDs) and inborn errors of immunity (IEI) can cause immune dysregulation, manifesting as lymphoproliferative and/or autoimmune disease. Autoimmunity can be the prominent phenotype of PIDs and commonly includes cytopenias and rheumatological diseases, such as arthritis, systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS). Recent advances in understanding the genetic basis of systemic autoimmune diseases and PIDs suggest an at least partially shared genetic background and therefore common pathogenic mechanisms. Here, we explore the interconnected pathogenic pathways of autoimmunity and primary immunodeficiency, highlighting the mechanisms breaking the different layers of immune tolerance to self-antigens in selected IEI.
Selective reaction of conjugated polymers with basic proteins for broad-spectrum antivirulence therapy
Authors: Sun Han , Liu Jing , Lv Fengting , Liu Libing , Gu Qi , Hu Baoyang , Wang Shu 
Published: April 2021

AbstractAntivirulence therapy has proven to be an attractive method for the treatment of bacterial infections and venomous injuries; however, the approaches for neutralizing multiple types of virulence through one platform are limited. To address this challenge, we have developed a reactive conjugated polymer, PPV–NHS, which functions as a broad-spectrum antidote for directly inactivating basic toxins. The antivirulence is achieved via multivalent electrostatic recognition and subsequent amidation reactions between PPV–NHS and toxins. The resultant bioconjugates significantly reduced neurotoxicity and cytotoxicity. In the mouse model, PPV–NHS effectively inhibited the toxicity of cardiotoxin (CTX) and improved the survival rate of toxin-challenged mice. This work represents the rational design of functionalized conjugated polymers for antivirulence therapy with both high efficiency and broad applicability.
Electrospun nanofiber-based soft electronics
Authors: Wang Yan , Yokota Tomoyuki , Someya Takao 
Published: April 2021

AbstractElectrospun nanofibers have received considerable attention in the field of soft electronics owing to their promising advantages and superior properties in flexibility and/or stretchability, conductivity, and transparency; furthermore, their one-dimensional nanostructure, high surface area, and diverse fibrous morphologies are also desirable. Herein, we provide an overview of electrospun nanofiber-based soft electronics. A brief introduction of the unique structure and properties of electrospun nanofiber materials is provided, and assembly strategies for flexible/stretchable electronics are highlighted. We then summarize the latest progress in the design and fabrication of representative flexible/stretchable electronic devices utilizing electrospun nanofibers, such as flexible/stretchable conductors, sensors, energy harvesting and storage devices, and transistors. Finally, a conclusion and several future research directions for electrospun nanofiber-based soft electronics are proposed.
Electrochemically active materials and wearable biosensors for the in situ analysis of body fluids for human healthcare
Authors: Park Heun , Park Woohyun , Lee Chi Hwan 
Published: April 2021

AbstractThe increasing demand for minimal to noninvasive in situ analysis of body fluids, such as sweat, interstitial fluid, and tears, has driven rapid development of electrochemically active materials and wearable biosensors. The mechanically soft and deformable nature of these biosensors enables them to efficiently adapt to the geometric nonlinearity of a specific part of the human body. The integration of these biosensors with a fully miniaturized wireless telemetry system enables displaying real-time data in a mobile device and/or reporting to an encrypted server for post analysis. These features are essential for the long-term, unobtrusive monitoring of biochemical activity in ambulatory care settings for improved management of many chronic diseases, such as diabetes, gout, and Parkinson’s disease. Herein, we present the latest innovations of wearable electrochemical sensors tailored for human skin or eyes with a focus on their materials, designs, sensing mechanisms, and clinical implications.
NIR-responsive MXene nanobelts for wound healing
Authors: Jin Lin , Guo Xiaoqing , Gao Di , Wu Cui , Hu Bin , Tan Guangxuan , Du Nannan , Cai Xiaolu , Yang Zhe , Zhang Xingcai 
Published: April 2021

AbstractEffectively achieving wound healing is a great challenge. Herein, we facilely prepared temperature-responsive MXene nanobelt fibers (T-RMFs) carrying vitamin E with a controllable release ability for wound healing. These T-RMFs were composed of MXene nanosheets spread along polyacrylonitrile and polyvinylpyrrolidone composite nanobelts together with a thermosensitive PAAV- coating layer. The high mass loading and high surface area of the MXene nanosheets endow the T-RMFs with excellent photothermal properties. The temperature could be easily controlled by near-infrared (NIR) irradiation exposure, and then the thermoresponsive polymeric coating layer relaxed the interface to dissolve vitamin E and promote vitamin E release. The T-RMFs demonstrated excellent biocompatibility and wound-healing functions in cellular and animal tests. The facile method, high mass loading, high surface area, excellent wound-healing functions, interesting nanosheet/nanobelt structure, mass production potential, and NIR responsive properties of these T-RMFs indicate the great potential of our nanobelts for wound healing, tissue engineering, and much broader application areas. This facile nanosheet/nanobelt preparation strategy paves a new way for nanomaterial fabrication and applications.
Evolution of DNA methylation in the human brain
Authors: Jeong Hyeonsoo , Mendizabal Isabel , Berto Stefano , Chatterjee Paramita , Layman Thomas , Usui Noriyoshi , Toriumi Kazuya , Douglas Connor , Singh Devika , Huh Iksoo , Preuss Todd M. , Konopka Genevieve , Yi Soojin V. 
Published: April 2021

AbstractDNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases.
Monocyte progenitors give rise to multinucleated giant cells
Authors: Lösslein Anne Kathrin , Lohrmann Florens , Scheuermann Lisa , Gharun Kourosh , Neuber Jana , Kolter Julia , Forde Aaron James , Kleimeyer Christian , Poh Ying Yee , Mack Matthias , Triantafyllopoulou Antigoni , Dunlap Micah D. , Khader Shabaana A. , Seidl Maximilian , Hölscher Alexandra , Hölscher Christoph , Guan Xue Li , Dorhoi Anca , Henneke Philipp 
Published: April 2021

AbstractThe immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche.
A polymer controlled nucleation route towards the generalized growth of organic-inorganic perovskite single crystals
Authors: Ma Lin , Yan Zhengguang , Zhou Xiaoyuan , Pi Yiqun , Du Yiping , Huang Jie , Wang Kaiwen , Wu Ke , Zhuang Chunqiang , Han Xiaodong 
Published: April 2021

AbstractRecently, there are significant progresses in the growth of organic-inorganic lead halide perovskite single crystals, however, due to their susceptible nucleation and growth mechanisms and solvent requirements, the efficient and generalized growth for these single crystals is still challenging. Here we report the work towards this target with a polymer-controlled nucleation process for the highly efficient growth of large-size high-quality simple ternary, mixed-cations and mixed-halide perovskite single crystals. Among them, the carrier lifetime of FAPbBr3 single crystals is largely improved to 10199 ns. Mixed MA/FAPbBr3 single crystals are synthesized. The crucial point in this process is suggested to be an appropriate coordinative interaction between polymer oxygen groups and Pb2+, greatly decreasing the nuclei concentrations by as much as 4 orders of magnitudes. This polymer-controlled route would help optimizing the solution-based OIHPs crystal growth and promoting applications of perovskite single crystals.
Systems serology detects functionally distinct coronavirus antibody features in children and elderly
Authors: Selva Kevin J. , van de Sandt Carolien E. , Lemke Melissa M. , Lee Christina Y. , Shoffner Suzanne K. , Chua Brendon Y. , Davis Samantha K. , Nguyen Thi H. O. , Rowntree Louise C. , Hensen Luca , Koutsakos Marios , Wong Chinn Yi , Mordant Francesca , Jackson David C. , Flanagan Katie L. , Crowe Jane , Tosif Shidan , Neeland Melanie R. , Sutton Philip , Licciardi Paul V. , Crawford Nigel W. , Cheng Allen C. , Doolan Denise L. , Amanat Fatima , Krammer Florian , Chappell Keith , Modhiran Naphak , Watterson Daniel , Young Paul , Lee Wen Shi , Wines Bruce D. , Mark Hogarth P. , Esterbauer Robyn , Kelly Hannah G. , Tan Hyon-Xhi , Juno Jennifer A. , Wheatley Adam K. , Kent Stephen J. , Arnold Kelly B. , Kedzierska Katherine , Chung Amy W. 
Published: April 2021

AbstractThe hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.
Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration
Authors: Ding Xin , Wang Jin , Huang Miaoxin , Chen Zhangpeng , Liu Jing , Zhang Qipeng , Zhang Chenyu , Xiang Yang , Zen Ke , Li Liang 
Published: April 2021

AbstractMicroglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.
Giant gauge factor of Van der Waals material based strain sensors
Authors: Yan Wenjie , Fuh Huei-Ru , Lv Yanhui , Chen Ke-Qiu , Tsai Tsung-Yin , Wu Yuh-Renn , Shieh Tung-Ho , Hung Kuan-Ming , Li Juncheng , Zhang Duan , Ó Coileáin Cormac , Arora Sunil K. , Wang Zhi , Jiang Zhaotan , Chang Ching-Ray , Wu Han-Chun 
Published: April 2021

AbstractThere is an emergent demand for high-flexibility, high-sensitivity and low-power strain gauges capable of sensing small deformations and vibrations in extreme conditions. Enhancing the gauge factor remains one of the greatest challenges for strain sensors. This is typically limited to below 300 and set when the sensor is fabricated. We report a strategy to tune and enhance the gauge factor of strain sensors based on Van der Waals materials by tuning the carrier mobility and concentration through an interplay of piezoelectric and photoelectric effects. For a SnS2 sensor we report a gauge factor up to 3933, and the ability to tune it over a large range, from 23 to 3933. Results from SnS2, GaSe, GeSe, monolayer WSe2, and monolayer MoSe2 sensors suggest that this is a universal phenomenon for Van der Waals semiconductors. We also provide proof of concept demonstrations by detecting vibrations caused by sound and capturing body movements.
Nectin-4 and p95-ErbB2 cooperatively regulate Hippo signaling-dependent SOX2 gene expression, enhancing anchorage-independent T47D cell proliferation
Authors: Kedashiro Shin , Kameyama Takeshi , Mizutani Kiyohito , Takai Yoshimi 
Published: April 2021

AbstractNectin-4, upregulated in various cancer cells, cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, p95-ErbB2 and ErbB2∆Ex16, enhancing DNA synthesis through the PI3K-AKT signaling in human breast cancer T47D cells in an adherent culture. We found here that nectin-4 and p95-ErbB2, but not nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively enhanced SOX2 gene expression and cell proliferation in a suspension culture. This enhancement of T47D cell proliferation in a suspension culture by nectin-4 and p95-ErbB2 was dependent on the SOX2 gene expression. In T47D cells, nectin-4 and any one of p95-ErbB2, ErbB2, or ErbB2∆Ex16 cooperatively activated the PI3K-AKT signaling, known to induce the SOX2 gene expression, to similar extents. However, only a combination of nectin-4 and p95-ErbB2, but not that of nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively enhanced the SOX2 gene expression. Detailed studies revealed that only nectin-4 and p95-ErbB2 cooperatively activated the Hippo signaling. YAP inhibited the SOX2 gene expression in this cell line and thus the MST1/2-LATS1/2 signaling-mediated YAP inactivation increased the SOX2 gene expression. These results indicate that only the combination of nectin-4 and p95-ErbB2, but not that of nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively regulates the Hippo signaling-dependent SOX2 gene expression, enhancing anchorage-independent T47D cell proliferation.
Motor learning deficits in cervical dystonia point to defective basal ganglia circuitry
Authors: Loens Sebastian , Verrel Julius , Herrmann Vera-Maria , Kienzle Amrei , Tzvi Elinor , Weissbach Anne , Junker Johanna , Münchau Alexander , Bäumer Tobias 
Published: April 2021

AbstractDystonia is conceptualized as a network disorder involving basal ganglia, thalamus, sensorimotor cortex and the cerebellum. The cerebellum has been implicated in dystonia pathophysiology, but studies testing cerebellar function in dystonia patients have provided equivocal results. This study aimed to further elucidate motor network deficits in cervical dystonia with special interest in the role of the cerebellum. To this end we investigated motor learning tasks, that differ in their dependence on cerebellar and basal ganglia functioning. In 18 cervical dystonia patients and 18 age matched healthy controls we measured implicit motor sequence learning using a 12-item serial reaction time task mostly targeting basal ganglia circuitry and motor adaptation and eyeblink conditioning as markers of cerebellar functioning. ANOVA showed that motor sequence learning was overall impaired in cervical dystonia (p = 0.01). Moreover, unlike healthy controls, patients did not show a learning effect in the first part of the experiment. Visuomotor adaptation and eyeblink conditioning were normal. In conclusion, these data lend support to the notion that motor learning deficits in cervical dystonia relate to basal ganglia-thalamo-cortical loops rather than being a result of defective cerebellar circuitry.