bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy blockade and lysosomal membrane permeabilization contribute to lead-induced nephrotoxicity in primary rat proximal tubular cells
Authors: Song Xiang-Bin , Liu Gang , Liu Fei , Yan Zhen-Gui , Wang Zhen-Yong , Liu Zong-Ping , Wang Lin 
Published: June 2017

AbstractLead (Pb) is a known nephrotoxicant that causes damage to proximal tubular cells. Autophagy has an important protective role in various renal injuries, but the role of autophagy in Pb-elicited nephrotoxicity remains largely unknown. In this study, Pb promoted the accumulation of autophagosomes in primary rat proximal tubular (rPT) cells, and subsequent findings revealed that this autophagosome accumulation was caused by the inhibition of autophagic flux. Moreover, Pb exposure did not affect the autophagosome–lysosome fusion in rPT cells. Next, we found that Pb caused lysosomal alkalinization, may be through suppression of two V-ATPase subunits. Simultaneously, Pb inhibited lysosomal degradation capacity by affecting the maturation of cathepsin B (CTSB) and cathepsin D (CTSD). Furthermore, translocation of CTSB and CTSD from lysosome to cytoplasm was observed in this study, suggesting that lysosomal membrane permeabilization (LMP) occurred in Pb-exposed rPT cells. Meanwhile, Pb-induced caspase-3 activation and apoptosis were significantly but not completely inhibited by CTSB inhibitor (CA 074) and CTSD inhibitor (pepstatin A), respectively, demonstrating that LMP-induced lysosomal enzyme release was involved in Pb-induced apoptosis in rPT cells. In conclusion, Pb-mediated autophagy blockade in rPT cells is attributed to the impairment of lysosomal function. Both inhibition of autophagic flux and LMP-mediated apoptosis contribute to Pb-induced nephrotoxicity in rPT cells.
Loss of the novel mitochondrial protein FAM210B promotes metastasis via PDK4-dependent metabolic reprogramming
Authors: Sun Shujuan , Liu Jia , Zhao Meisong , Han Yingyan , Chen Pingbo , Mo Qingqing , Wang Beibei , Chen Gang , Fang Yong , Tian Yuan , Zhou Jianfeng , Ma Ding , Gao Qinglei , Wu Peng 
Published: June 2017

AbstractRecent advances in tumor metabolism have revealed that metabolic reprogramming could dramatically promote caner metastasis. However, the relation and mechanism between metastasis and metabolic reprogramming are not thoroughly explored. Cell proliferation, colony formation, and invasion analysis were performed to evaluate the role of FAM210B in human cancer cells. Human ovarian cancer xenograft model was used to determine the effects of inhibiting FAM210B by shRNA on tumor metastasis. Microarray analysis was used to determine the target genes of FAM210B. FAM210B cellular localization was performed by mitochondria isolation and mitochondria protein extraction. To detect FAM210B-mediated metabolic reprogramming, oxygen consumption rate and extracellular acidification rate were measured. Our previous study screened a novel cancer progression-suppressor gene, FAM210B, which encodes an outer mitochondrial membrane protein, by the suppression of mortality by antisense rescue technique (SMART). Here we demonstrated that FAM210B loss was significantly associated with cancer metastasis and decreased survival in a clinical setting. Additionally, it was found that low expression of FAM210B was significantly correlated with decreased survival and enhanced metastasis in vivo and in vitro, and the loss of FAM210B led to an increased mitochondrial respiratory capacity and reduced glycolysis through the downregulation of pyruvate dehydrogenase kinase 4 (PDK4), which activated the EMT program and enhanced migratory and invasive properties. Collectively, our data unveil a potential metabolic target and mechanism of cancer metastasis.
Loss of Asxl2 leads to myeloid malignancies in mice
Authors: Li Jianping , He Fuhong , Zhang Peng , Chen Shi , Shi Hui , Sun Yanling , Guo Ying , Yang Hui , Man Na , Greenblatt Sarah , Li Zhaomin , Guo Zhengyu , Zhou Yuan , Wang Lan , Morey Lluis , Williams Sion , Chen Xi , Wang Qun-Tian , Nimer Stephen D. , Yu Peng , Wang Qian-Fei , Xu Mingjiang , Yang Feng-Chun 
Published: June 2017

AbstractASXL2 is frequently mutated in acute myeloid leukaemia patients with t(8;21). However, the roles of ASXL2 in normal haematopoiesis and the pathogenesis of myeloid malignancies remain unknown. Here we show that deletion of Asxl2 in mice leads to the development of myelodysplastic syndrome (MDS)-like disease. Asxl2−/− mice have an increased bone marrow (BM) long-term haematopoietic stem cells (HSCs) and granulocyte–macrophage progenitors compared with wild-type controls. Recipients transplanted with Asxl2−/− and Asxl2+/− BM cells have shortened lifespan due to the development of MDS-like disease or myeloid leukaemia. Paired daughter cell assays demonstrate that Asxl2 loss enhances the self-renewal of HSCs. Deletion of Asxl2 alters the expression of genes critical for HSC self-renewal, differentiation and apoptosis in Lin−cKit+ cells. The altered gene expression is associated with dysregulated H3K27ac and H3K4me1/2. Our study demonstrates that ASXL2 functions as a tumour suppressor to maintain normal HSC function.
Protein-directed ribosomal frameshifting temporally regulates gene expression
Authors: Napthine Sawsan , Ling Roger , Finch Leanne K. , Jones Joshua D. , Bell Susanne , Brierley Ian , Firth Andrew E. 
Published: June 2017

AbstractProgrammed −1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct a proportion of translating ribosomes to shift −1 nt and continue translating in the new reading frame. Such frameshifting normally occurs at a set ratio and is utilized in the expression of many viral genes and a number of cellular genes. An open question is whether proteins might function as trans-acting switches to turn frameshifting on or off in response to cellular conditions. Here we show that frameshifting in a model RNA virus, encephalomyocarditis virus, is trans-activated by viral protein 2A. As a result, the frameshifting efficiency increases from 0 to 70% (one of the highest known in a mammalian system) over the course of infection, temporally regulating the expression levels of the viral structural and enzymatic proteins.
Water pumping in mantle shear zones
Authors: Précigout Jacques , Prigent Cécile , Palasse Laurie , Pochon Anthony 
Published: June 2017

AbstractWater plays an important role in geological processes. Providing constraints on what may influence the distribution of aqueous fluids is thus crucial to understanding how water impacts Earth’s geodynamics. Here we demonstrate that ductile flow exerts a dynamic control on water-rich fluid circulation in mantle shear zones. Based on amphibole distribution and using dislocation slip-systems as a proxy for syn-tectonic water content in olivine, we highlight fluid accumulation around fine-grained layers dominated by grain-size-sensitive creep. This fluid aggregation correlates with dislocation creep-accommodated strain that localizes in water-rich layers. We also give evidence of cracking induced by fluid pressure where the highest amount of water is expected. These results emphasize long-term fluid pumping attributed to creep cavitation and associated phase nucleation during grain size reduction. Considering the ubiquitous process of grain size reduction during strain localization, our findings shed light on multiple fluid reservoirs in the crust and mantle.
Current-induced skyrmion generation and dynamics in symmetric bilayers
Authors: Hrabec A. , Sampaio J. , Belmeguenai M. , Gross I. , Weil R. , Chérif S. M. , Stashkevich A. , Jacques V. , Thiaville A. , Rohart S. 
Published: June 2017

AbstractMagnetic skyrmions are quasiparticle-like textures which are topologically different from other states. Their discovery in systems with broken inversion symmetry sparked the search for materials containing such magnetic phase at room temperature. Their topological properties combined with the chirality-related spin–orbit torques make them interesting objects to control the magnetization at nanoscale. Here we show that a pair of coupled skyrmions of opposite chiralities can be stabilized in a symmetric magnetic bilayer system by combining Dzyaloshinskii–Moriya interaction (DMI) and dipolar coupling effects. This opens a path for skyrmion stabilization with lower DMI. We demonstrate in a device with asymmetric electrodes that such skyrmions can be independently written and shifted by electric current at large velocities. The skyrmionic nature of the observed quasiparticles is confirmed by the gyrotropic force. These results set the ground for emerging spintronic technologies where issues concerning skyrmion stability, nucleation and propagation are paramount.
Dynamic contrast-enhanced photoacoustic imaging using photothermal stimuli-responsive composite nanomodulators
Authors: Chen Yun-Sheng , Yoon Soon Joon , Frey Wolfgang , Dockery Mary , Emelianov Stanislav 
Published: June 2017

AbstractMolecular photoacoustic imaging has shown great potential in medical applications; its sensitivity is normally in pico-to-micro-molar range, dependent on exogenous imaging agents. However, tissue can produce strong background signals, which mask the signals from the imaging agents, resulting in orders of magnitude sensitivity reduction. As such, an elaborate spectral scan is often required to spectrally un-mix the unwanted background signals. Here we show a new single-wavelength photoacoustic dynamic contrast-enhanced imaging technique by employing a stimuli-responsive contrast agent. Our technique can eliminate intrinsic background noises without significant hardware or computational resources. We show that this new contrast agent can generate up to 30 times stronger photoacoustic signals than the concentration-matched inorganic nanoparticle counterparts. By dynamically modulating signals from the contrast agents with an external near-infrared optical stimulus, we can further suppress the background signals leading to an additional increase of more than five-fold in imaging contrast in vivo.
Quantum annealing with all-to-all connected nonlinear oscillators
Authors: Puri Shruti , Andersen Christian Kraglund , Grimsmo Arne L. , Blais Alexandre 
Published: June 2017

AbstractQuantum annealing aims at solving combinatorial optimization problems mapped to Ising interactions between quantum spins. Here, with the objective of developing a noise-resilient annealer, we propose a paradigm for quantum annealing with a scalable network of two-photon-driven Kerr-nonlinear resonators. Each resonator encodes an Ising spin in a robust degenerate subspace formed by two coherent states of opposite phases. A fully connected optimization problem is mapped to local fields driving the resonators, which are connected with only local four-body interactions. We describe an adiabatic annealing protocol in this system and analyse its performance in the presence of photon loss. Numerical simulations indicate substantial resilience to this noise channel, leading to a high success probability for quantum annealing. Finally, we propose a realistic circuit QED implementation of this promising platform for implementing a large-scale quantum Ising machine.
Spatio-temporal variability of trace elements fingerprints in cockle (Cerastoderma edule) shells and its relevance for tracing geographic origin
Authors: Ricardo Fernando , Pimentel Tânia , Génio Luciana , Calado Ricardo 
Published: June 2017

AbstractUnderstanding spatio-temporal variability of trace elements fingerprints (TEF) in bivalve shells is paramount to determine the discrimination power of this analytical approach and secure traceability along supply chains. Spatio-temporal variability of TEF was assessed in cockle (Cerastoderma edule) shells using inductively coupled plasma-mass spectrometry (ICP-MS). Four elemental ratios (Mg/Ca, Mn/Ca, Sr/Ca and Ba/Ca) were measured from the shells of specimens originating from eight different ecosystems along the Portuguese coast, as well as from four different areas, within one of them, over two consecutive years (2013 and 2014). TEF varied significantly in the shells of bivalves originating from the eight ecosystems surveyed in the present study. Linear discriminant function analyses assigned sampled cockles to each of the eight ecosystems with an average accuracy of 90%. Elemental ratios also displayed significant differences between the two consecutive years in the four areas monitored in the same ecosystem. Overall, while TEF displayed by cockle shells can be successfully used to trace their geographic origin, a periodical verification of TEF (>6 months and <1 year) is required to control for temporal variability whenever comparing specimens originating from the same area collected more than six months apart.
Universal fractality of morphological transitions in stochastic growth processes
Authors: Nicolás-Carlock J. R. , Carrillo-Estrada J. L. , Dossetti V. 
Published: June 2017

AbstractStochastic growth processes give rise to diverse and intricate structures everywhere in nature, often referred to as fractals. In general, these complex structures reflect the non-trivial competition among the interactions that generate them. In particular, the paradigmatic Laplacian-growth model exhibits a characteristic fractal to non-fractal morphological transition as the non-linear effects of its growth dynamics increase. So far, a complete scaling theory for this type of transitions, as well as a general analytical description for their fractal dimensions have been lacking. In this work, we show that despite the enormous variety of shapes, these morphological transitions have clear universal scaling characteristics. Using a statistical approach to fundamental particle-cluster aggregation, we introduce two non-trivial fractal to non-fractal transitions that capture all the main features of fractal growth. By analyzing the respective clusters, in addition to constructing a dynamical model for their fractal dimension, we show that they are well described by a general dimensionality function regardless of their space symmetry-breaking mechanism, including the Laplacian case itself. Moreover, under the appropriate variable transformation this description is universal, i.e., independent of the transition dynamics, the initial cluster configuration, and the embedding Euclidean space.
Differential synchrotron X-ray imaging markers based on the renal microvasculature for tubulointerstitial lesions and glomerulopathy
Authors: Lin Yu-Chuan , Hwu Yeukuang , Huang Guo-Shu , Hsiao Michael , Lee Tsung-Tse , Yang Shun-Min , Lee Ting-Kuo , Chen Nan-Yow , Yang Sung-Sen , Chen Ann , Ka Shuk-Man 
Published: June 2017

AbstractHigh resolution synchrotron microtomography capable of revealing microvessels in three dimensional (3D) establishes distinct imaging markers of mouse kidney disease strongly associated to renal tubulointerstitial (TI) lesions and glomerulopathy. Two complementary mouse models of chronic kidney disease (CKD), unilateral ureteral obstruction (UUO) and focal segmental glomerulosclerosis (FSGS), were used and five candidates of unique 3D imaging markers were identified. Our characterization to differentially reflect the altered microvasculature of renal TI lesions and/or glomerulopathy demonstrated these image features can be used to differentiate the disease status and the possible cause therefore qualified as image markers. These 3D imaging markers were further correlated with the histopathology and renal microvessel-based molecular study using antibodies against vascular endothelial cells (CD31), the connective tissue growth factor or the vascular endothelial growth factor. We also found that these 3D imaging markers individually characterize the development of renal TI lesions or glomerulopathy, quantitative and integrated use of all of them provide more information for differentiating the two renal conditions. Our findings thus establish a practical strategy to characterize the CKD-associated renal injuries by the microangiography-based 3D imaging and highlight the impact of dysfunctional microvasculature as a whole on the pathogenesis of the renal lesions.
Improved retinal function in RCS rats after suppressing the over-activation of mGluR5
Authors: Dai Jiaman , Fu Yan , Zeng Yuxiao , Li Shiying , Qin Yin Zheng 
Published: June 2017

AbstractMüller cells maintain retinal synaptic homeostasis by taking up glutamate from the synaptic cleft and transporting glutamine back to the neurons. To study the interaction between Müller cells and photoreceptors, we injected either DL-α-aminoadipate or L-methionine sulfoximine–both inhibitors of glutamine synthetase–subretinally in rats. Following injection, the a-wave of the electroretinogram (ERG) was attenuated, and metabotropic glutamate receptor 5 (mGluR5) was activated. Selective antagonism of mGluR5 by 2-methyl-6-(phenylethynyl)-pyridine increased the ERG a-wave amplitude and also increased rhodopsin expression. Conversely, activation of mGluR5 by the agonist, (R,S)-2-chloro-5-hydroxyphenylglycine, decreased both the a-wave amplitude and rhodopsin expression, but upregulated expression of Gq alpha subunit and phospholipase C βIII. Overexpression of mGluR5 reduced the inward-rectifying potassium ion channel (Kir) current and decreased the expression of Kir4.1 and aquaporin-4 (AQP4). Further experiments indicated that mGluR5 formed a macromolecular complex with these two membrane channels. Lastly, increased expression of mGluR5 was found in Royal College of Surgeons rats–a model of retinitis pigmentosa (RP). Inhibition of mGluR5 in this model restored the amplitude of ERG features, and reduced the expression of glial fibrillary acidic protein. These results suggest that mGluR5 may be worth considering as a potential therapeutic target in RP.
The CCAAT-Binding Complex Controls Respiratory Gene Expression and Iron Homeostasis in Candida Glabrata
Authors: Thiébaut Antonin , Delaveau Thierry , Benchouaia Médine , Boeri Julia , Garcia Mathilde , Lelandais Gaëlle , Devaux Frédéric 
Published: June 2017

AbstractThe CCAAT-binding complex (CBC) is a heterotrimeric transcription factor which is widely conserved in eukaryotes. In the model yeast S. cerevisiae, CBC positively controls the expression of respiratory pathway genes. This role involves interactions with the regulatory subunit Hap4. In many pathogenic fungi, CBC interacts with the HapX regulatory subunit to control iron homeostasis. HapX is a bZIP protein which only shares with Hap4 the Hap4Like domain (Hap4L) required for its interaction with CBC. Here, we show that CBC has a dual role in the pathogenic yeast C. glabrata. It is required, along with Hap4, for the constitutive expression of respiratory genes and it is also essential for the iron stress response, which is mediated by the Yap5 bZIP transcription factor. Interestingly, Yap5 contains a vestigial Hap4L domain. The mutagenesis of this domain severely reduced Yap5 binding to its targets and compromised its interaction with Hap5. Hence, Yap5, like HapX in other species, acts as a CBC regulatory subunit in the regulation of iron stress response. This work reveals new aspects of iron homeostasis in C. glabrata and of the evolution of the role of CBC and Hap4L-bZIP proteins in this process.
Oestrogen Inhibits Arterial Calcification by Promoting Autophagy
Authors: Peng Yi-Qun , Xiong Dan , Lin Xiao , Cui Rong-Rong , Xu Feng , Zhong Jia-Yu , Zhu Ting , Wu Feng , Mao Min-Zhi , Liao Xiao-Bo , Yuan Ling-Qing 
Published: June 2017

AbstractArterial calcification is a major complication of cardiovascular disease. Oestrogen replacement therapy in postmenopausal women is associated with lower levels of coronary artery calcification, but its mechanism of action remains unclear. Here, we show that oestrogen inhibits the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) in vitro and arterial calcification in vivo by promoting autophagy. Through electron microscopy, GFP–LC3 redistribution, and immunofluorescence analyses as well as measurement of the expression of the autophagosome marker light-chain I/II (LC3I/II) and autophagy protein 5 (Atg5), we show that autophagy is increased in VSMCs by oestrogen in vitro and in vivo. The inhibitory effect of oestrogen on arterial calcification was counteracted by 3-methyladenine (3MA) or knockdown of Atg5 and was increased by rapamycin. Furthermore, the inhibitory effect of oestrogen on arterial calcification and the degree of autophagy induced by oestrogen were blocked by a nonselective oestrogen receptor (ER) antagonist (ICI 182780), a selective oestrogen receptor alpha (ERα) antagonist (MPP), and ERα-specific siRNA. Our data indicate that oestrogen inhibits the osteoblastic differentiation of VSMCs by promoting autophagy through the ERα signalling pathway in vitro and arterial calcification in vivo by increasing autophagy. Our findings provide new insights into the mechanism by which oestrogen contributes to vascular calcification in vitro and in vivo.
Urban conservation hotspots: predation release allows the grassland-specialist burrowing owl to perform better in the city
Authors: Rebolo-Ifrán Natalia , Tella José L. , Carrete Martina 
Published: June 2017

AbstractAlthough habitat transformation is one of the main causes of biodiversity loss, there are many examples of species successfully occupying and even proliferating in highly human-modified habitats such are the cities. Thus, there is an increasing interest in understanding the drivers favoring urban life for some species. Here, we show how the low richness and abundance of predators in urban areas may explain changes in the habitat selection pattern of a grassland specialist species, the burrowing owlAthene cunicularia, toward urban habitats. Predation release improves the demographic parameters of urban individuals, thus favoring an increment in the breeding density of the species in urban areas that accounts for the apparent positive selection of this habitat in detriment of the more natural ones that are avoided. These results suggest that traditional habitat selection analyses do not necessarily describe habitat choice decisions actively taken by individuals but differences in their demographic prospects. Moreover, they also highlight that cites, as predator-free refuges, can become key conservation hotspots for some species dependent on threatened habitats such as the temperate grasslands of South America.