bluuebunny/crossref_metadata_2025_split huggingface dataset:
U-box ubiquitin ligase PPIL2 suppresses breast cancer invasion and metastasis by altering cell morphology and promoting SNAI1 ubiquitination and degradation
Authors: Jia Zhaojun , Wang Miao , Li Shujing , Li Xiahui , Bai Xiao-Yan , Xu Zhaowei , Yang Yangyang , Li Bowen , Li Yanan , Wu Huijian 
Published: January 2018

AbstractMetastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear. Herein, we demonstrate that PPIL2 suppressed metastasis in a breast cancer model by altering cell morphology and suppressing the epithelial–mesenchymal transition (EMT) process. Moreover, elevated PPIL2 inhibited EMT and breast cancer invasion by interacting with the classical EMT transcription factor, SNAI1, to enhance its ubiquitin-dependent degradation. Furthermore, PPIL2 protein level and stability was upregulated after CsA treatment, indicating that PPIL2 might be involved in CsA-mediated repression of EMT in breast cancer. Analysis of tissue samples taken from breast cancer patients showed a significant correlation between the expression of PPIL2 and the degree of cancer invasion and metastasis. In summary, these results would shed light on a potential clinical use of CsA in breast cancer patients.
STIL balancing primary microcephaly and cancer
Authors: Patwardhan Dhruti , Mani Shyamala , Passemard Sandrine , Gressens Pierre , El Ghouzzi Vincent 
Published: January 2018

Abstract
Cell division and differentiation are two fundamental physiological processes that need to be tightly balanced to achieve harmonious development of an organ or a tissue without jeopardizing its homeostasis. The role played by the centriolar protein STIL is highly illustrative of this balance at different stages of life as deregulation of the human STIL gene expression has been associated with either insufficient brain development (primary microcephaly) or cancer, two conditions resulting from perturbations in cell cycle and chromosomal segregation. This review describes the recent advances on STIL functions in the control of centriole duplication and mitotic spindle integrity, and discusses how pathological perturbations of its finely tuned expression result in chromosomal instability in both embryonic and postnatal situations, highlighting the concept that common key factors are involved in developmental steps and tissue homeostasis.
SWELL1 is a glucose sensor regulating β-cell excitability and systemic glycaemia
Authors: Kang Chen , Xie Litao , Gunasekar Susheel K. , Mishra Anil , Zhang Yanhui , Pai Saachi , Gao Yiwen , Kumar Ashutosh , Norris Andrew W. , Stephens Samuel B. , Sah Rajan 
Published: January 2018

AbstractInsulin secretion is initiated by activation of voltage-gated Ca2+ channels (VGCC) to trigger Ca2+-mediated insulin vesicle fusion with the β-cell plasma membrane. The firing of VGCC requires β-cell membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (ICl,SWELL) in both murine and human β-cells. Hypotonic and glucose-stimulated β-cell swelling activates SWELL1-mediated ICl,SWELL and this contributes to membrane depolarization and activation of VGCC-dependent intracellular calcium signaling. SWELL1 depletion in MIN6 cells and islets significantly impairs glucose-stimulated insulin secretion. Tamoxifen-inducible β-cell-targeted Swell1 KO mice have normal fasting serum glucose and insulin levels but impaired glucose-stimulated insulin secretion and glucose tolerance; and this is further exacerbated in mild obesity. Our results reveal that β-cell SWELL1 modulates insulin secretion and systemic glycaemia by linking glucose-mediated β-cell swelling to membrane depolarization and activation of VGCC-triggered calcium signaling.
Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells
Authors: Tosic Milica , Allen Anita , Willmann Dominica , Lepper Christoph , Kim Johnny , Duteil Delphine , Schüle Roland 
Published: January 2018

AbstractSatellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.
Closed-loop stimulation of temporal cortex rescues functional networks and improves memory
Authors: Ezzyat Youssef , Wanda Paul A. , Levy Deborah F. , Kadel Allison , Aka Ada , Pedisich Isaac , Sperling Michael R. , Sharan Ashwini D. , Lega Bradley C. , Burks Alexis , Gross Robert E. , Inman Cory S. , Jobst Barbara C. , Gorenstein Mark A. , Davis Kathryn A. , Worrell Gregory A. , Kucewicz Michal T. , Stein Joel M. , Gorniak Richard , Das Sandhitsu R. , Rizzuto Daniel S. , Kahana Michael J. 
Published: January 2018

AbstractMemory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target for memory enhancement. Taken together, our results suggest that such systems may provide a therapeutic approach for treating memory dysfunction.
The creation of electric wind due to the electrohydrodynamic force
Authors: Park Sanghoo , Cvelbar Uros , Choe Wonho , Moon Se Youn 
Published: January 2018

AbstractUnderstanding the interactions between ionized matter and neutral particles is a prerequisite for discovering their impact on natural phenomena. One such phenomenon is the electric wind, which supposedly occurs due to the charged particle–neutral coupling in systems of weakly ionized gases, but this mechanism remains unclear. Here, we report direct evidence that electric wind is caused by an electrohydrodynamic force generated by the charged particle drag as a result of the momentum transfer from electrons/ions to neutrals. The model experiment is based on a pulsed plasma jet as a source of weakly ionized gases generated in the helium gas at atmospheric pressure using Schlieren photography. Studying the helium gas flow trajectories at different discharge parameters allows one to distinguish between the effects of streamer propagation or space charge drift causing the electric wind as well as to determine the role of electrons and (positive) ions in wind generation.
The ecological origins of snakes as revealed by skull evolution
Authors: Da Silva Filipe O. , Fabre Anne-Claire , Savriama Yoland , Ollonen Joni , Mahlow Kristin , Herrel Anthony , Müller Johannes , Di-Poï Nicolas 
Published: January 2018

AbstractThe ecological origin of snakes remains amongst the most controversial topics in evolution, with three competing hypotheses: fossorial; marine; or terrestrial. Here we use a geometric morphometric approach integrating ecological, phylogenetic, paleontological, and developmental data for building models of skull shape and size evolution and developmental rate changes in squamates. Our large-scale data reveal that whereas the most recent common ancestor of crown snakes had a small skull with a shape undeniably adapted for fossoriality, all snakes plus their sister group derive from a surface-terrestrial form with non-fossorial behavior, thus redirecting the debate toward an underexplored evolutionary scenario. Our comprehensive heterochrony analyses further indicate that snakes later evolved novel craniofacial specializations through global acceleration of skull development. These results highlight the importance of the interplay between natural selection and developmental processes in snake origin and diversification, leading first to invasion of a new habitat and then to subsequent ecological radiations.
AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation
Authors: Gélinas Roselle , Mailleux Florence , Dontaine Justine , Bultot Laurent , Demeulder Bénédicte , Ginion Audrey , Daskalopoulos Evangelos P. , Esfahani Hrag , Dubois-Deruy Emilie , Lauzier Benjamin , Gauthier Chantal , Olson Aaron K. , Bouchard Bertrand , Des Rosiers Christine , Viollet Benoit , Sakamoto Kei , Balligand Jean-Luc , Vanoverschelde Jean-Louis , Beauloye Christophe , Horman Sandrine , Bertrand Luc 
Published: January 2018

AbstractAMP-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte hypertrophy without affecting downstream targets previously suggested to be involved, such as p70 ribosomal S6 protein kinase, calcineurin/nuclear factor of activated T cells (NFAT) and extracellular signal-regulated kinases. Instead, cardiomyocyte hypertrophy is accompanied by increased protein O-GlcNAcylation, which is reversed by AMPK activation. Decreasing O-GlcNAcylation by inhibitors of the glutamine:fructose-6-phosphate aminotransferase (GFAT), blocks cardiomyocyte hypertrophy, mimicking AMPK activation. Conversely, O-GlcNAcylation-inducing agents counteract the anti-hypertrophic effect of AMPK. In vivo, AMPK activation prevents myocardial hypertrophy and the concomitant rise of O-GlcNAcylation in wild-type but not in AMPKα2-deficient mice. Treatment of wild-type mice with O-GlcNAcylation-inducing agents reverses AMPK action. Finally, we demonstrate that AMPK inhibits O-GlcNAcylation by mainly controlling GFAT phosphorylation, thereby reducing O-GlcNAcylation of proteins such as troponin T. We conclude that AMPK activation prevents cardiac hypertrophy predominantly by inhibiting O-GlcNAcylation.
Pervasive Rise of Small-scale Deforestation in Amazonia
Authors: Kalamandeen Michelle , Gloor Emanuel , Mitchard Edward , Quincey Duncan , Ziv Guy , Spracklen Dominick , Spracklen Benedict , Adami Marcos , Aragão Luiz E. O. C. , Galbraith David 
Published: January 2018

AbstractUnderstanding forest loss patterns in Amazonia, the Earth’s largest rainforest region, is critical for effective forest conservation and management. Following the most detailed analysis to date, spanning the entire Amazon and extending over a 14-year period (2001–2014), we reveal significant shifts in deforestation dynamics of Amazonian forests. Firstly, hotspots of Amazonian forest loss are moving away from the southern Brazilian Amazon to Peru and Bolivia. Secondly, while the number of new large forest clearings (>50 ha) has declined significantly over time (46%), the number of new small clearings (<1 ha) increased by 34% between 2001–2007 and 2008–2014. Thirdly, we find that small-scale low-density forest loss expanded markedly in geographical extent during 2008–2014. This shift presents an important and alarming new challenge for forest conservation, despite reductions in overall deforestation rates.
PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance of Tregs in the skin
Authors: Miao Xiao , Xu Rong , Fan Bin , Chen Jie , Li Xin , Mao Weiwei , Hua Shengyuan , Li Bin 
Published: January 2018

AbstractProgrammed cell death 1 ligand 1 (PD-L1) is a ligand of programmed cell death 1 (PD-1) that functions as an immune checkpoint by down-regulating immune responses. To determine whether PD-L1 is a therapy target in vitiligo treatment, Pmel-1 vitiligo mice were treated with a PD-L1 fusion protein. Treatment with this fusion protein significantly reversed/suppressed depigmentation development in adult Pmel-1 mice. Mechanistically, enrichment of regulatory T cells (Treg) in the skin was detected after PD-L1 fusion protein treatment in Pmel-1 mice. Furthermore, Tregs abundance was also increased in both the spleen and circulation of Pmel-1 mice treated with PD-L1. These data indicate that PD-L1 protein therapy inhibits the immune response and reverses depigmentation development in Pmel-1 vitiligo mice.
Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation
Authors: Croft Sarah N. , Walker Erin J. , Ghildyal Reena 
Published: January 2018

AbstractHuman Rhinovirus (HRV) is a pathogen of significant medical importance, being a major cause of upper respiratory tract infections (common colds) as well as causing the majority of virus-induced asthma exacerbations. We investigated whether HRV could modulate apoptosis, an innate antiviral response. Apoptotic signals are generated either extrinsically or intrinsically and are propagated via caspase cascades that lead to cell death, reducing viral replication, which relies on cellular machinery. Using HRV16 infected cells, in combination with chemical inducers and inhibitors of extrinsic apoptosis we show that HRV16 3C protease cleaves a key intermediate in extrinsic apoptosis. Receptor-interacting protein kinase-1 (RIPK1), an extrinsic apoptosis adaptor protein, was cleaved by caspase 8, as expected, during chemical induction of apoptosis. RIPK1 was cleaved in HRV infection albeit at a different site. Caspase 8 activation, which is associated with extrinsic apoptosis, was concurrent with HRV 3C protease mediated cleavage of RIPK1, and potentially increased the accessibility of the HRV 3C cleavage site within RIPK1 in-vitro. The caspase 8 mediated RIPK1 cleavage product has a pro-apoptotic function, and further cleavage of this pro-apoptotic cleavage product by HRV 3C may provide a mechanism by which HRV limits apoptosis.
Simultaneous bilateral total knee arthroplasty in patients with end-stage hemophilic arthropathy: a mean follow-up of 6 years
Authors: Jiang Chao , Zhao Yan , Feng Bin , Zhai Jiliang , Bian Yanyan , Qiu Guixing , Weng Xisheng 
Published: January 2018

AbstractTo investigate the safety, cost-effectiveness, and clinical outcomes of simultaneous bilateral total knee arthroplasty (TKA) in hemophilic arthropathy (HA), the requirements for transfusions, complications, costs, hospital stays, Hospital for Special Surgery (HSS) knee scores, knee range of motion (ROM) and revision rates were compared between simultaneous bilateral and unilateral TKA in HA patients. A total of 36 patients and 54 knees were included. Compared to the unilateral group, the bilateral group did not require more transfusions (2.39 ± 3.13 vs 0.83 ± 1.38 units of RBCs, p > 0.05) or consumption of coagulation factors (50091.67 ± 25168.5 vs 46477.78 ± 11348.32 IU, p > 0.05), complications rate (13/36 vs 6/18, p > 0.05), hospital stay (32.39 ± 19.77 vs 29.11 ± 12.67 days, p > 0.05), or costs excluding prostheses (14945.41 ± 6634.35 vs 14742.12 ± 5746.78 US dollars, p > 0.05). Additionally, the two groups exhibited similar medium-term knee HSS scores (83.67 ± 7.11 vs 81.00 ± 10.35, p > 0.05) and ROM (89.39° ± 13.66° vs 88.91° ± 12.90°, p > 0.05). Our data indicate that bilateral TKA is a safe and cost-effective treatment for HA with similar medium-term results compared to unilateral TKA.
The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia
Authors: Vecino Rebeca , Burguete Maria C. , Jover-Mengual Teresa , Agulla Jesus , Bobo-Jiménez Verónica , Salom Juan B. , Almeida Angeles , Delgado-Esteban Maria 
Published: January 2018

AbstractBrain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat brain (in vivo). Our results show that PC increased neuronal MDM2 protein levels, which prevented ischemia-induced p53 stabilization and neuronal death. Indeed, PC attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2-p53 pathway was confirmed in rat brain using a PC model in vivo. These findings demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection against a subsequent ischemic insult and poses MDM2 as an essential target in ischemic tolerance.
Alternating Droplet Formation by using Tapered Channel Geometry
Authors: Saqib Muhammad , Şahinoğlu O. Berkay , Erdem E. Yegân 
Published: January 2018

AbstractThe ability to produce a controlled sequence of alternating droplets from two separate sources inside a microfluidic system brings several advantages in microfluidic analysis. The effectiveness of this technique for use in an application depends on the ability of the device to replicate the pattern continuously and accurately. In this work we studied the effect of the dispersed phase channel geometry on generating a repeating pattern of alternating droplets in a cross junction microfluidic device. By measuring the radius of curvature of a droplet at the time of break up, and calculating the Laplace pressure using these values, we analyzed how the angle of taper of the dispersed phase inlet channel has an influence on the pattern repetition and uniformity of formed droplet size and spacing in between. The performance of devices with different angle of taper values were studied experimentally. This comparative study indicated that the ability of a cross junction device to generate alternating droplets with uniform size and spacing is highly dependent on the angle of taper of the inlet channels; and it improves with larger taper angles.
Contrasting temperature trends across the ice-free part of Greenland
Authors: Westergaard-Nielsen Andreas , Karami Mojtaba , Hansen Birger Ulf , Westermann Sebastian , Elberling Bo 
Published: January 2018

AbstractTemperature changes in the Arctic have notable impacts on ecosystem structure and functioning, on soil carbon dynamics, and on the stability of permafrost, thus affecting ecosystem functions and putting man-built infrastructure at risk. Future warming in the Arctic could accelerate important feedbacks in permafrost degradation processes. Therefore it is important to map vulnerable areas most likely to be impacted by temperature changes and at higher risk of degradation, particularly near communities, to assist adaptation to climate change. Currently, these areas are poorly assessed, especially in Greenland. Here we quantify trends in satellite-derived land surface temperatures and modelled air temperatures, validated against observations, across the entire ice-free Greenland. Focus is on the past 30 years, to characterize significant changes and potentially vulnerable regions at a 1 km resolution. We show that recent temperature trends in Greenland vary significantly between seasons and regions and that data with resolutions down to single km2 are critical to map temperature changes for guidance of further local studies and decision-making. Only a fraction of the ice-free Greenland seems vulnerable due to warming when analyzing year 2001–2015, but the most pronounced changes are found in the most populated parts of Greenland. As Greenland represents important gradients of north/south coast/inland/distance to large ice sheets, the conclusions are also relevant in an upscaling to greater Arctic areas.
Maximising wind generation through optimised operation of on‐load tap changing transformers in active distribution networks
Authors: Danzerl Daniel , Gill Simon , Anaya‐Lara Olimpo 
Published: January 2018

On‐load tap changing transformers are the most common control device to regulate and maintain distribution network voltage within required limits. Voltage rise issues on the other hand have become a major factor limiting greater penetration of low carbon generators, particularly in weak distribution networks. Here, the voltage rise problem is addressed through the application of optimised set‐point voltage technique that aims to improve network hosting capacity to accommodate high wind penetration. It assesses the effectiveness of the technique on a realistic 289‐node UK generic 11 kV distribution network using time‐series optimal power flow simulations. The results reveal that when the tap changer is operated at the optimised set‐point voltage, it can lead to greater energy yields. It also shows a reduction in the number of tap changing operations when the transformer is operated within the optimised deadband allowing for an improved life‐span and minimum maintenance cost.