bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posttranslational arginylation enzyme Ate1 affects DNA mutagenesis by regulating stress response
Authors: Kumar Akhilesh , Birnbaum Michael D , Patel Devang M , Morgan William M , Singh Jayanti , Barrientos Antoni , Zhang Fangliang 
Published: September 2016

AbstractArginyltransferase 1 (Ate1) mediates protein arginylation, a poorly understood protein posttranslational modification (PTM) in eukaryotic cells. Previous evidence suggest a potential involvement of arginylation in stress response and this PTM was traditionally considered anti-apoptotic based on the studies of individual substrates. However, here we found that arginylation promotes cell death and/or growth arrest, depending on the nature and intensity of the stressing factor. Specifically, in yeast, mouse and human cells, deletion or downregulation of the ATE1 gene disrupts typical stress responses by bypassing growth arrest and suppressing cell death events in the presence of disease-related stressing factors, including oxidative, heat, and osmotic stresses, as well as the exposure to heavy metals or radiation. Conversely, in wild-type cells responding to stress, there is an increase of cellular Ate1 protein level and arginylation activity. Furthermore, the increase of Ate1 protein directly promotes cell death in a manner dependent on its arginylation activity. Finally, we found Ate1 to be required to suppress mutation frequency in yeast and mammalian cells during DNA-damaging conditions such as ultraviolet irradiation. Our study clarifies the role of Ate1/arginylation in stress response and provides a new mechanism to explain the link between Ate1 and a variety of diseases including cancer. This is also the first example that the modulation of the global level of a PTM is capable of affecting DNA mutagenesis.
miRNA-558 promotes gastric cancer progression through attenuating Smad4-mediated repression of heparanase expression
Authors: Zheng Liduan , Jiao Wanju , Song Huajie , Qu Hongxia , Li Dan , Mei Hong , Chen Yajun , Yang Feng , Li Huanhuan , Huang Kai , Tong Qiangsong 
Published: September 2016

AbstractPrevious studies have indicated that as the only mammalian endo-β-D-glucuronidase, heparanase (HPSE) is up-regulated and associated with poor prognosis in gastric cancer, while the underlying mechanisms still remain to be determined. Herein, through integrative analysis of public datasets, we found microRNA-558 (miR-558) and SMAD family member 4 (Smad4) as the crucial transcription regulators of HPSE expression in gastric cancer, with their adjacent target sites within the promoter of HPSE. We identified that endogenous miR-558 activated the transcription and expression of HPSE in gastric cancer cell lines. In contrast, Smad4 suppressed the nascent transcription and expression of HPSE via directly binding to its promoter. Mechanistically, miR-558 recognized its complementary site within HPSE promoter to decrease the binding of Smad4 in an Argonaute 1-dependent manner. Ectopic expression or knockdown experiments indicated that miR-558 promoted the in vitro and in vivo tumorigenesis and aggressiveness of gastric cancer cell lines via attenuating Smad4-mediated repression of HPSE expression. In clinical gastric cancer specimens, up-regulation of miR-558 and down-regulation of Smad4 were positively correlated with HPSE expression. Kaplan–Meier survival analysis revealed that miR-558 and Smad4 were associated with unfavourable and favourable outcome of gastric cancer patients, respectively. Therefore, these findings demonstrate that miR-558 facilitates the progression of gastric cancer through directly targeting the HPSE promoter to attenuate Smad4-mediated repression of HPSE expression.
Quantized conductance doubling and hard gap in a two-dimensional semiconductor–superconductor heterostructure
Authors: Kjaergaard M. , Nichele F. , Suominen H. J. , Nowak M. P. , Wimmer M. , Akhmerov A. R. , Folk J. A. , Flensberg K. , Shabani J. , Palmstrøm C. J. , Marcus C. M. 
Published: September 2016

AbstractCoupling a two-dimensional (2D) semiconductor heterostructure to a superconductor opens new research and technology opportunities, including fundamental problems in mesoscopic superconductivity, scalable superconducting electronics, and new topological states of matter. One route towards topological matter is by coupling a 2D electron gas with strong spin–orbit interaction to an s-wave superconductor. Previous efforts along these lines have been adversely affected by interface disorder and unstable gating. Here we show measurements on a gateable InGaAs/InAs 2DEG with patterned epitaxial Al, yielding devices with atomically pristine interfaces between semiconductor and superconductor. Using surface gates to form a quantum point contact (QPC), we find a hard superconducting gap in the tunnelling regime. When the QPC is in the open regime, we observe a first conductance plateau at 4e2/h, consistent with theory. The hard-gap semiconductor–superconductor system demonstrated here is amenable to top-down processing and provides a new avenue towards low-dissipation electronics and topological quantum systems.
Young asteroidal fluid activity revealed by absolute age from apatite in carbonaceous chondrite
Authors: Zhang Ai-Cheng , Li Qiu-Li , Yurimoto Hisayoshi , Sakamoto Naoya , Li Xian-Hua , Hu Sen , Lin Yang-Ting , Wang Ru-Cheng 
Published: September 2016

AbstractChondritic meteorites, consisting of the materials that have formed in the early solar system (ESS), have been affected by late thermal events and fluid activity to various degrees. Determining the timing of fluid activity in ESS is of fundamental importance for understanding the nature, formation, evolution and significance of fluid activity in ESS. Previous investigations have determined the relative ages of fluid activity with short-lived isotope systematics. Here we report an absolute207Pb/206Pb isochron age (4,450±50 Ma) of apatite from Dar al Gani (DaG) 978, a type ∼3.5, ungrouped carbonaceous chondrite. The petrographic, mineralogical and geochemical features suggest that the apatite in DaG 978 should have formed during metamorphism in the presence of a fluid. Therefore, the apatite age represents an absolute age for fluid activity in an asteroidal setting. An impact event could have provided the heat to activate this young fluid activity in ESS.
Aromatic thiol-mediated cleavage of N–O bonds enables chemical ubiquitylation of folded proteins
Authors: Weller Caroline E. , Dhall Abhinav , Ding Feizhi , Linares Edlaine , Whedon Samuel D. , Senger Nicholas A. , Tyson Elizabeth L. , Bagert John D. , Li Xiaosong , Augusto Ohara , Chatterjee Champak 
Published: September 2016

AbstractAccess to protein substrates homogenously modified by ubiquitin (Ub) is critical for biophysical and biochemical investigations aimed at deconvoluting the myriad biological roles for Ub. Current chemical strategies for protein ubiquitylation, however, employ temporary ligation auxiliaries that are removed under harsh denaturing conditions and have limited applicability. We report an unprecedented aromatic thiol-mediated N–O bond cleavage and its application towards native chemical ubiquitylation with the ligation auxiliary 2-aminooxyethanethiol. Our interrogation of the reaction mechanism suggests a disulfide radical anion as the active species capable of cleaving the N–O bond. The successful semisynthesis of full-length histone H2B modified by the small ubiquitin-like modifier-3 (SUMO-3) protein further demonstrates the generalizability and compatibility of our strategy with folded proteins.
ICER is requisite for Th17 differentiation
Authors: Yoshida Nobuya , Comte Denis , Mizui Masayuki , Otomo Kotaro , Rosetti Florencia , Mayadas Tanya N. , Crispín José C. , Bradley Sean J. , Koga Tomohiro , Kono Michihito , Karampetsou Maria P. , Kyttaris Vasileios C. , Tenbrock Klaus , Tsokos George C. 
Published: September 2016

AbstractInducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6–STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4+ T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane-induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4+ T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17-dependent manner.
Should the diagnosis of COPD be based on a single spirometry test?
Authors: Schermer Tjard R , Robberts Bas , Crockett Alan J , Thoonen Bart P , Lucas Annelies , Grootens Joke , Smeele Ivo J , Thamrin Cindy , Reddel Helen K 
Published: September 2016

AbstractClinical guidelines indicate that a chronic obstructive pulmonary disease (COPD) diagnosis is made from a single spirometry test. However, long-term stability of diagnosis based on forced expiratory volume in 1 s over forced vital capacity (FEV1/FVC) ratio has not been reported. In primary care subjects at risk for COPD, we investigated shifts in diagnostic category (obstructed/non-obstructed). The data were from symptomatic 40+ years (ex-)smokers referred for diagnostic spirometry, with three spirometry tests, each 12±2 months apart. The obstruction was based on post-bronchodilator FEV1/FVC < lower limit of normal (LLN) and <0.70 (fixed ratio). A total of 2,352 subjects (54% male, post-bronchodilator FEV1 76.5% predicted) were studied. By LLN definition, 32.2% were obstructed at baseline, but 32.2% of them were no longer obstructed at years 1 and/or 2. By fixed ratio, these figures were 46.6 and 23.8%, respectively. Overall, 14.3% of subjects changed diagnostic category by 1 year and 15.4% by 2 years when applying the LLN cut-off, and 15.1 and 14.6% by fixed ratio. Change from obstructed to non-obstructed was more likely for patients with higher body mass index (BMI) and baseline short-acting bronchodilator (SABA) users, and less likely for older subjects, those with lower FEV1% predicted, baseline inhaled steroid users, and current smokers or SABA users at year 1. Change from non-obstructed to obstructed was more likely for males, older subjects, current smokers and patients with lower baseline FEV1% predicted, and less likely for those with higher baseline BMI. Up to one-third of symptomatic (ex-)smokers with baseline obstruction on diagnostic spirometry had shifted to non-obstructed when routinely re-tested after 1 or 2 years. Given the implications for patients and health systems of a diagnosis of COPD, it should not be based on a single spirometry test.
Interplay between cell cycle and autophagy induced by boswellic acid analog
Authors: Pathania Anup S. , Guru Santosh K. , Kumar Suresh , Kumar Ashok , Ahmad Masroor , Bhushan Shashi , Sharma Parduman R. , Mahajan Priya , Shah Bhahwal A. , Sharma Simmi , Nargotra Amit , Vishwakarma Ram , Korkaya Hasan , Malik Fayaz 
Published: September 2016

AbstractIn this study, we investigated the role of autophagy induced by boswellic acid analog BA145 on cell cycle progression in pancreatic cancer cells. BA145 induced robust autophagy in pancreatic cancer cell line PANC-1 and exhibited cell proliferation inhibition by inducing cells to undergo G2/M arrest. Inhibition of G2/M progression was associated with decreased expression of cyclin A, cyclin B, cyclin E, cdc2, cdc25c and CDK-1. Pre-treatment of cells with autophagy inhibitors or silencing the expression of key autophagy genes abrogated BA145 induced G2/M arrest and downregulation of cell cycle regulatory proteins. It was further observed that BA145 induced autophagy by targeting mTOR kinase (IC50 1 μM), leading to reduced expression of p-mTOR, p-p70S6K (T389), p-4EBP (T37/46) and p-S6 (S240/244). Notably, inhibition of mTOR signalling by BA145 was followed by attendant activation of AKT and its membrane translocation. Inhibition of Akt through pharmacological inhibitors or siRNAs enhanced BA145 mediated autophagy, G2/M arrest and reduced expression of G2/M regulators. Further studies revealed that BA145 arbitrated inhibition of mTOR led to the activation of Akt through IGFR/PI3k/Akt feedback loop. Intervention in IGFR/PI3k/Akt loop further depreciated Akt phosphorylation and its membrane translocation that culminates in augmented autophagy with concomitant G2/M arrest and cell death.
Cell biology is different in small volumes: endogenous signals shape phenotype of primary hepatocytes cultured in microfluidic channels
Authors: Haque Amranul , Gheibi Pantea , Gao Yandong , Foster Elena , Son Kyung Jin , You Jungmok , Stybayeva Gulnaz , Patel Dipali , Revzin Alexander 
Published: September 2016

AbstractThe approaches for maintaining hepatocytes in vitro are aimed at recapitulating aspects of the native liver microenvironment through the use of co-cultures, surface coatings and 3D spheroids. This study highlights the effects of spatial confinement-a less studied component of the in vivo microenvironment. We demonstrate that hepatocytes cultured in low-volume microfluidic channels (microchambers) retain differentiated hepatic phenotype for 21 days whereas cells cultured in regular culture plates under identical conditions de-differentiate after 7 days. Careful consideration of nutrient delivery and oxygen tension suggested that these factors could not solely account for enhanced cell function in microchambers. Through a series of experiments involving microfluidic chambers of various heights and inhibition of key molecular pathways, we confirmed that phenotype of hepatocytes in small volumes was shaped by endogenous signals, both hepato-inductive growth factors (GFs) such as hepatocyte growth factor (HGF) and hepato-disruptive GFs such as transforming growth factor (TGF)-β1. Hepatocytes are not generally thought of as significant producers of GFs–this role is typically assigned to nonparenchymal cells of the liver. Our study demonstrates that, in an appropriate microenvironment, hepatocytes produce hepato-inductive and pro-fibrogenic signals at the levels sufficient to shape their phenotype and function.
Genomic Selection Improves Heat Tolerance in Dairy Cattle
Authors: Garner J. B. , Douglas M. L. , Williams S. R. O , Wales W. J. , Marett L. C. , Nguyen T. T. T. , Reich C. M. , Hayes B. J. 
Published: September 2016

AbstractDairy products are a key source of valuable proteins and fats for many millions of people worldwide. Dairy cattle are highly susceptible to heat-stress induced decline in milk production, and as the frequency and duration of heat-stress events increases, the long term security of nutrition from dairy products is threatened. Identification of dairy cattle more tolerant of heat stress conditions would be an important progression towards breeding better adapted dairy herds to future climates. Breeding for heat tolerance could be accelerated with genomic selection, using genome wide DNA markers that predict tolerance to heat stress. Here we demonstrate the value of genomic predictions for heat tolerance in cohorts of Holstein cows predicted to be heat tolerant and heat susceptible using controlled-climate chambers simulating a moderate heatwave event. Not only was the heat challenge stimulated decline in milk production less in cows genomically predicted to be heat-tolerant, physiological indicators such as rectal and intra-vaginal temperatures had reduced increases over the 4 day heat challenge. This demonstrates that genomic selection for heat tolerance in dairy cattle is a step towards securing a valuable source of nutrition and improving animal welfare facing a future with predicted increases in heat stress events.
A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force
Authors: Bano Fouzia , Banerji Suneale , Howarth Mark , Jackson David G. , Richter Ralf P. 
Published: September 2016

AbstractGlycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.
Band Gap Engineering of Two-Dimensional Nitrogene
Authors: Li Jie-Sen , Wang Wei-Liang , Yao Dao-Xin 
Published: September 2016

AbstractIn our previous study, we have predicted the novel two-dimensional honeycomb monolayers of pnictogen. In particular, the structure and properties of the honeycomb monolayer of nitrogen, which we call nitrogene, are very unusual. In this paper, we make an in-depth investigation of its electronic structure. We find that the band structure of nitrogene can be engineered in several ways: controlling the stacking of monolayers, application of biaxial tensile strain, and application of perpendicular electric field. The band gap of nitrogene is found to decrease with the increasing number of layers. The perpendicular electric field can also reduce the band gap when it is larger than 0.18 V/Å, and the gap closes at 0.35 V/Å. A nearly linear dependence of the gap on the electric field is found during the process. Application of biaxial strain can decrease the band gap as well, and eventually closes the gap. After the gap-closing, we find six inequivalent Dirac points in the Brillouin zone under the strain between 17% and 28%, and the nitrogene monolayer becomes a Dirac semimetal. These findings suggest that the electronic structure of nitrogene can be modified by several techniques, which makes it a promising candidate for electronic devices.
Large low field magnetocaloric effect in first-order phase transition compound TlFe3Te3 with low-level hysteresis
Authors: Mao Qianhui , Yang Jinhu , Wang Hangdong , Khan Rajwali , Du Jianhua , Zhou Yuxing , Xu Binjie , Chen Qin , Fang Minghu 
Published: September 2016

AbstractMagnetic refrigeration based on the magnetocaloric effect (MCE) is an environment-friendly, high-efficiency technology. It has been believed that a large MCE can be realized in the materials with a first-order magnetic transition (FOMT). Here, we found that TlFe3Te3 is a ferromagnetic metal with a first-order magnetic transition occurring at Curie temperature TC = 220 K. The maximum values of magnetic entropy change (Δ"Equation missing") along the crystallographic c-axis, estimated from the magnetization data, reach to 5.9 J kg−1K−1 and 7.0 J kg−1 K−1 for the magnetic field changes, ΔH = 0–1 T and 0–2 T, respectively, which is significantly larger than that of MCE materials with a second-order magnetic transition (SOMT). Besides the large ΔSM, the low-level both thermal and field hysteresis make TlFe3Te3 compound an attractive candidate for magnetic refrigeration. Our findings should inspire the exploration of high performance new MCE materials.
Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury
Authors: Chen Yu-Li , Hwang Tsong-Long , Yu Huang-Ping , Fang Jia-You , Chong Kowit Yu , Chang Yao-Wen , Chen Chun-Yu , Yang Hsuan-Wu , Chang Wen-Yi , Hsieh Pei-Wen 
Published: September 2016

AbstractAcute lung injury (ALI) is a severe respiratory disease with high mortality rates worldwide. Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy. In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs). Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC50, 11.37 ± 1.59 μg/mL). Using bioactivity-guided fractionation, one new compound and 23 known compounds were identified. Compound 6 (identified as 3,5-dicaffeoylquinic acid; 3,5-DCQA) exerted the most potent and selective inhibitory effect on HNE activity (IC50, 1.86 ± 0.06 μM). In a cell-based assay, 3,5-DCQA not only directly reduced superoxide generation and elastase activity but also attenuated the Src family kinase (SRKs)/Vav signaling pathway in N-formyl-L-Met-L-Leu-L-Phe (fMLF)-stimulated human neutrophils. In an animal disease model, both 3,5-DCQA and standardized IKWE protected against lipopolysaccharide-induced ALI in mice, which provides support for their potential as candidates in the development of new therapeutic agents for neutrophilic inflammatory diseases.
Identity information content depends on the type of facial movement
Authors: Dobs Katharina , Bülthoff Isabelle , Schultz Johannes 
Published: September 2016

AbstractFacial movements convey information about many social cues, including identity. However, how much information about a person’s identity is conveyed by different kinds of facial movements is unknown. We addressed this question using a recent motion capture and animation system, with which we animated one avatar head with facial movements of three types: (1) emotional, (2) emotional in social interaction and (3) conversational, all recorded from several actors. In a delayed match-to-sample task, observers were best at matching actor identity across conversational movements, worse with emotional movements in social interactions, and at chance level with emotional facial expressions. Model observers performing this task showed similar performance profiles, indicating that performance variation was due to differences in information content, rather than processing. Our results suggest that conversational facial movements transmit more dynamic identity information than emotional facial expressions, thus suggesting different functional roles and processing mechanisms for different types of facial motion.