bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone deacetylase 10 structure and molecular function as a polyamine deacetylase
Authors: Hai Yang , Shinsky Stephen A. , Porter Nicholas J. , Christianson David W. 
Published: May 2017

AbstractCationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo sapiens (human) and Danio rerio (zebrafish). The 2.85 Å-resolution crystal structure of zebrafish HDAC10 complexed with a transition-state analogue inhibitor reveals that a glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Both HDAC10 and spermidine are known to promote cellular survival through autophagy. Accordingly, this work sets a foundation for studying the chemical biology of autophagy through the structure-based design of inhibitors that may also serve as new leads for cancer chemotherapy.
ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia
Authors: Micol Jean-Baptiste , Pastore Alessandro , Inoue Daichi , Duployez Nicolas , Kim Eunhee , Lee Stanley Chun-Wei , Durham Benjamin H. , Chung Young Rock , Cho Hana , Zhang Xiao Jing , Yoshimi Akihide , Krivtsov Andrei , Koche Richard , Solary Eric , Sinha Amit , Preudhomme Claude , Abdel-Wahab Omar 
Published: May 2017

AbstractAdditional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, little is known about its paralog ASXL2, which is frequently mutated in acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 is required for normal haematopoiesis with distinct, non-overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor. While Asxl2 was required for normal haematopoietic stem cell self-renewal, Asxl2 loss promoted AML1-ETO leukemogenesis. Moreover, ASXL2 target genes strongly overlapped with those of RUNX1 and AML1-ETO and ASXL2 loss was associated with increased chromatin accessibility at putative enhancers of key leukemogenic loci. These data reveal that Asxl2 is a critical regulator of haematopoiesis and mediates transcriptional effects that promote leukemogenesis driven by AML1-ETO.
Artificial local magnetic field inhomogeneity enhances T2 relaxivity
Authors: Zhou Zijian , Tian Rui , Wang Zhenyu , Yang Zhen , Liu Yijing , Liu Gang , Wang Ruifang , Gao Jinhao , Song Jibin , Nie Liming , Chen Xiaoyuan 
Published: May 2017

AbstractClustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau–Lifshitz–Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents.
Selective BET bromodomain inhibition as an antifungal therapeutic strategy
Authors: Mietton Flore , Ferri Elena , Champleboux Morgane , Zala Ninon , Maubon Danièle , Zhou Yingsheng , Harbut Mike , Spittler Didier , Garnaud Cécile , Courçon Marie , Chauvel Murielle , d’Enfert Christophe , Kashemirov Boris A. , Hull Mitchell , Cornet Muriel , McKenna Charles E. , Govin Jérôme , Petosa Carlo 
Published: May 2017

AbstractInvasive fungal infections cause significant morbidity and mortality among immunocompromised individuals, posing an urgent need for new antifungal therapeutic strategies. Here we investigate a chromatin-interacting module, the bromodomain (BD) from the BET family of proteins, as a potential antifungal target in Candida albicans, a major human fungal pathogen. We show that the BET protein Bdf1 is essential in C. albicans and that mutations inactivating its two BDs result in a loss of viability in vitro and decreased virulence in mice. We report small-molecule compounds that inhibit C. albicans Bdf1 with high selectivity over human BDs. Crystal structures of the Bdf1 BDs reveal binding modes for these inhibitors that are sterically incompatible with the human BET-binding pockets. Furthermore, we report a dibenzothiazepinone compound that phenocopies the effects of a Bdf1 BD-inactivating mutation on C. albicans viability. These findings establish BET inhibition as a promising antifungal therapeutic strategy and identify Bdf1 as an antifungal drug target that can be selectively inhibited without antagonizing human BET function.
Heat guiding and focusing using ballistic phonon transport in phononic nanostructures
Authors: Anufriev Roman , Ramiere Aymeric , Maire Jeremie , Nomura Masahiro 
Published: May 2017

AbstractUnlike classical heat diffusion at macroscale, nanoscale heat conduction can occur without energy dissipation because phonons can ballistically travel in straight lines for hundreds of nanometres. Nevertheless, despite recent experimental evidence of such ballistic phonon transport, control over its directionality, and thus its practical use, remains a challenge, as the directions of individual phonons are chaotic. Here, we show a method to control the directionality of ballistic phonon transport using silicon membranes with arrays of holes. First, we demonstrate that the arrays of holes form fluxes of phonons oriented in the same direction. Next, we use these nanostructures as directional sources of ballistic phonons and couple the emitted phonons into nanowires. Finally, we introduce thermal lens nanostructures, in which the emitted phonons converge at the focal point, thus focusing heat into a spot of a few hundred nanometres. These results motivate the concept of ray-like heat manipulations at the nanoscale.
Spectral correlations in a random distributed feedback fibre laser
Authors: Sugavanam Srikanth , Sorokina Mariia , Churkin Dmitry V. 
Published: May 2017

AbstractRandom distributed feedback fibre lasers belong to the class of random lasers, where the feedback is provided by amplified Rayleigh scattering on sub-micron refractive index inhomogenities randomly distributed over the fibre length. Despite the elastic nature of Rayleigh scattering, the feedback mechanism has been insofar deemed incoherent, which corresponds to the commonly observed smooth generation spectra. Here, using a real-time spectral measurement technique based on a scanning Fabry-Pérot interferometer, we observe long-living narrowband components in the random fibre laser’s spectrum. Statistical analysis of the ∼104 single-scan spectra reveals a preferential interspacing for the components and their anticorrelation in intensities. Furthermore, using mutual information analysis, we confirm the existence of nonlinear correlations between different parts of the random fibre laser spectra. The existence of such narrowband spectral components, together with their observed correlations, establishes a long-missing parallel between the fields of random fibre lasers and conventional random lasers.
Signal recognition particle prevents N-terminal processing of bacterial membrane proteins
Authors: Ranjan Amitabh , Mercier Evan , Bhatt Arshiya , Wintermeyer Wolfgang 
Published: May 2017

AbstractBacterial proteins are synthesized with an N-formylated amino-terminal methionine, and N-formylated peptides elicit innate-immunity responses against bacterial infections. However, the source of these formylated peptides is not clear, as most bacterial proteins are co-translationally deformylated by peptide deformylase. Here we develop a deformylation assay with translating ribosomes as substrates, to show that the binding of the signal recognition particle (SRP) to signal sequences in nascent proteins on the ribosome prevents deformylation, whereas deformylation of nascent proteins without signal sequence is not affected. Deformylation and its inhibition by SRP are not influenced by trigger factor, a chaperone that interacts with nascent chains on the ribosome. We propose that bacterial inner-membrane proteins, in particular those with N-out topology, can retain their N-terminal formyl group during cotranslational membrane insertion and supply formylated peptides during bacterial infections.
Natural Convection Flow of a Nanofluid in an Inclined Square Enclosure Partially Filled with a Porous Medium
Authors: Alsabery A. I. , Chamkha A. J. , Saleh H. , Hashim I. 
Published: May 2017

AbstractThis work analyses free convection flow of a nanofluid in an inclined square enclosure consisting of a porous layer and a nanofluid layer using the finite difference methodology. Sinusoidal temperature boundary conditions are imposed on the two opposing vertical walls. Nanofluids with water as base and Ag or Cu or Al2O3 or TiO2 nanoparticles are considered for the problem. The related parameters of this study are the Darcy number, nanoparticle volume fraction, phase deviation, amplitude ratio, porous layer thickness and the inclination angle of the cavity. A comparison with previously published work is performed and the results are in good agreement. Detailed numerical data for the fluid flow and thermal distributions inside the square enclosure, and the Nusselt numbers are presented. The obtained results show that the heat transfer is considerably affected by the porous layer increment. Several nanoparticles depicted a diversity improvement on the convection heat transfer.
A seven-million-year hornblende mineral record from the central Chinese Loess Plateau
Authors: He Tong , Liu Lianwen , Chen Yang , Sheng Xuefen , Ji Junfeng 
Published: May 2017

AbstractPrevious studies of the late Cenozoic erosion rate have yielded different views—long-term stable rates or a significant increase at climate transitions—leading to uncertainty concerning the hypothesized global erosion rate controlled by either tectonic uplift or climatic changes. Here, we present a seven-million-year hornblende mineral record along the Lingtai section of the Chinese Loess Plateau. By examining the spatial distribution of hornblende minerals in seven desert basins, which are potential loess source areas, we constructed a ratio of hornblende versus total heavy minerals to reflect past changes in physical/chemical weathering strength. Our results demonstrate that the ratio has generally increased since 7 Ma, with three significant shifts recorded at 2.6 Ma, 1.4 Ma and 0.5 Ma linked to the onset, continuation and expansion of the Northern Hemisphere glaciation, respectively. Given that chemical weathering during the diagenetic history produces a trend of smoothly increasing hornblende migrating upwards, the three shifts at these boundaries can be interpreted as changes in the bedrock erosion rate on the northern Tibetan Plateau, which may be related to tectonic uplift events and incision of the Yellow River. Evidence presented here supports the idea of coupling between climate change, tectonic uplift and regional erosion.
Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome
Authors: Qi Yuekun , Li Xiao , Chang Chunkang , Xu Feng , He Qi , Zhao Youshan , Wu Lingyun 
Published: May 2017

AbstractRibosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression is associated with abnormal apoptotic resistance in CD34+ cells derived from patients with higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced apoptotic resistance in higher-risk MDS patients is poorly understood. In this study, we showed that reduced RPL23 expression led to suppressed cellular viability, increased apoptosis and G1-S cell cycle arrest. Gene microarray analysis comparing RPL23-knockdown and control cells identified an array of differentially expressed genes, of which, Miz-1, was upregulated with transactivation of the cell cycle inhibitors p15Ink4band p21Cip1, and Miz-1’s functional repressor, c-Myc, was downregulated. Cells derived from higher-risk MDS patients demonstrated consistently increased expression of RPL23 and c-Myc and decreased Miz-1 expression compared with cells from lower-risk patients. In conclusion, Miz-1-dependent induction of p15Ink4band p21Cip1was depressed with decreased Miz-1 and increased c-Myc expression under conditions of elevated RPL23 expression, leading to apoptotic resistance in higher-risk MDS patients. Because RPL23 is encoded by a target gene of c-Myc, the RPL23/Miz-1/c-Myc regulatory circuit provides a feedback loop that links efficient RPL23 expression with c-Myc’s function to suppress Miz-1-induced Cdk inhibitors and thereby leads to apoptotic resistance in higher-risk MDS patients.
Hunger enhances consistent economic choices in non-human primates
Authors: Yamada Hiroshi 
Published: May 2017

AbstractHunger and thirst are fundamental biological processes that drive consumption behavior in humans and non-human animals. While the existing literature in neuroscience suggests that these satiety states change how consumable rewards are represented in the brain, it remains unclear as to how they change animal choice behavior and the underlying economic preferences. Here, I used combined techniques from experimental economics, psychology, and neuroscience to measure food preferences of marmoset monkeys (Callithrix jacchus), a recently developed primate model for neuroscience. Hunger states of animals were manipulated by scheduling feeding intervals, resulting in three different conditions: sated, non-sated, and hungry. During these hunger states, animals performed pairwise choices of food items, which included all possible pairwise combinations of five different food items except for same-food pairs. Results showed that hunger enhanced economic rationality, evident as a decrease of transitivity violations (item A was preferred to item B, and B to C, but C was preferred to A). Further analysis demonstrated that hungry monkeys chose more-preferred items over less-preferred items in a more deterministic manner, while the individual food preferences appeared to remain stable across hunger states. These results suggest that hunger enhances consistent choice behavior and shifts animals towards efficient outcome maximization.
Combinatory Evaluation of Transcriptome and Metabolome Profiles of Low Temperature-induced Resistant Ascites Syndrome in Broiler Chickens
Authors: Shi Shourong , Shen Yiru , Zhang Shan , Zhao Zhenhua , Hou Zhuocheng , Zhou Huaijun , Zou Jianmin , Guo Yuming 
Published: May 2017

AbstractTo select metabolic biomarkers and differentially expressed genes (DEGs) associated with resistant-ascites syndrome (resistant-AS), we used innovative techniques such as metabolomics and transcriptomics to comparatively examine resistant-AS chickens and AS controls. Metabolomic evaluation of chicken serum using ultra-performance liquid chromatography-quadruple time-of-flight high-sensitivity mass spectrometry (UPLC-QTOF/HSMS) showed significantly altered lysoPC(18:1), PE(18:3/16:0), PC(20:1/18:3), DG(24:1/22:6/0:0), PS(18:2/18:0), PI(16:0/16:0), PS(18:0/18:1), PS(14:1/14:0), dihydroxyacetone, ursodeoxycholic acid, tryptophan, L-valine, cycloserine, hypoxanthine, and 4-O-Methylmelleolide concentrations on day 21 and LysoPC(18:0), LysoPE(20:1/0:0), LysoPC(16:0), LysoPE(16:0/0:0), hypoxanthine, dihydroxyacetone, 4-O-Methylmelleolide, LysoPC(18:2), and PC(14:1/22:1) concentrations on day 35, between the susceptible and resistant groups. Compared to the susceptible group, transcriptomic analysis of liver samples using RNA-seq revealed 413 DEGs on day 21 and 214 DEGs on day 35 in the resistant group. Additional evaluations using gene ontology (GO) indicate that significant enrichment occurred in the oxygen transportation, defensive reactions, and protein modifications of the decreased DEGs as well as in the cell morphological formation, neural development, and transforming growth factor (TGF)-beta signalling of the increased DEGs on day 21. Oxygen transportation was also significantly enriched for downregulated DEGs on day 35. The combinatory evaluation of the metabolome and the transcriptome suggests the possible involvement of glycerophospholipid metabolism in the development of resistant-AS in broilers.
Functional compressive mechanics and tissue biocompatibility of an injectable SF/PU hydrogel for nucleus pulposus replacement
Authors: Hu Jingen , Lu Yang , Cai Ling , Owusu-Ansah Kwabena Gyabaah , Xu Gewen , Han Feilong , Bao Junjie , Lin Xiangjin , Huang Yiping 
Published: May 2017

AbstractIn spinal degenerative disease, an injectable liquid hydrogel can fill in defect entirely, lessen the danger of implant relocation and following loss of disc height, minimizing the operative trauma. Here, we propose an injectable in-situ chemically cross-linked hydrogel by a two-component reaction of liquid silk fibroin with liquid polyurethane at physiological temperature conditions. Confined compression tests and fatigue tests were reported to assess physical properties of the hydrogel. Impact of different diameter on the biomechanical behaviours was tested to evaluate the clinical potentiality of the hydrogel for replacing nucleus pulposus. Degradation behaviours in different solutions and animal experiments were also investigated to examine the tissue biocompatibility of the hydrogel. The hydrogel modulus was affected by the hydrogel geometrical (diameter) parameters. SF/PU composite hydrogel can survive a million cycles, unconstrained fatigue resistance. More importantly, in vivo biocompatibility using New Zealand white rabbits, showed good biocompatibility over a three-month period in culture. Particularly, they showed the significant clinical merit of providing stronger axial compressive stiffness on confined compression test. Based on the outcomes of the present research, the SF/PU composite hydrogel may provide significant advantages for use in future clinical application in replacing nucleus pulposus field.
Manipulation of Rat Movement via Nigrostriatal Stimulation Controlled by Human Visually Evoked Potentials
Authors: Koo Bonkon , Koh Chin Su , Park Hae-Yong , Lee Hwan-Gon , Chang Jin Woo , Choi Seungjin , Shin Hyung-Cheul 
Published: May 2017

AbstractHere, we report that the development of a brain-to-brain interface (BBI) system that enables a human user to manipulate rat movement without any previous training. In our model, the remotely-guided rats (known as ratbots) successfully navigated a T-maze via contralateral turning behaviour induced by electrical stimulation of the nigrostriatal (NS) pathway by a brain- computer interface (BCI) based on the human controller’s steady-state visually evoked potentials (SSVEPs). The system allowed human participants to manipulate rat movement with an average success rate of 82.2% and at an average rat speed of approximately 1.9 m/min. The ratbots had no directional preference, showing average success rates of 81.1% and 83.3% for the left- and right-turning task, respectively. This is the first study to demonstrate the use of NS stimulation for developing a highly stable ratbot that does not require previous training, and is the first instance of a training-free BBI for rat navigation. The results of this study will facilitate the development of borderless communication between human and untrained animals, which could not only improve the understanding of animals in humans, but also allow untrained animals to more effectively provide humans with information obtained with their superior perception.
Identification of the matricellular protein Fibulin-5 as a target molecule of glucokinase-mediated calcineurin/NFAT signaling in pancreatic islets
Authors: Okuyama Tomoko , Shirakawa Jun , Yanagisawa Hiromi , Kyohara Mayu , Yamazaki Shunsuke , Tajima Kazuki , Togashi Yu , Terauchi Yasuo 
Published: May 2017

AbstractGlucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The isletFbln5expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase inFbln5expression was diminished inIrs-2-deficient islets. GKA-inducedFbln5upregulation in the islets was blunted by a glucokinase inhibitor, KATPchannel opener, Ca2+channel blocker and calcineurin inhibitor, while it was augmented by harmine, a dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) 1 A inhibitor. Although deletion ofFbln5in mice had no significant effects on the glucose tolerance or β-cell functions, adenovirus-mediatedFbln5overexpression increased glucose-stimulated insulin secretion in INS-1 rat insulinoma cells. Since the islet Fbln5 expression is regulated through a glucokinase/KATPchannel/calcineurin/nuclear factor of activated T cells (NFAT) pathway crucial for the maintenance of β-cell functions, further investigation of Fbln5 functions in the islets is warranted.
Low level of Lck kinase in Th2 cells limits expression of CD4 co-receptor and S73 phosphorylation of transcription factor c-Jun
Authors: Shebzukhov Yury V. , Stanislawiak Silke , Bezhaeva Taisiya R. , Nedospasov Sergei A. , Kuprash Dmitry V. 
Published: May 2017

AbstractThe Src-family tyrosine kinase Lck is an enzyme associated with the CD4 and CD8 co-receptors and promoting signaling through the T cell receptor (TCR) complex. The levels of Lck expression and activity change during the development and differentiation of T cells. Here we show that Lck expression is higher in Th1 cells as compared to Th2 cells. Ectopic overexpression of Lck in Th2 cells results in increased expression of CD4 co-receptor and enhanced S73 phosphorylation of transcription factor c-Jun. Our findings indicate that TCR-mediated signaling in Th2 cells may be directly attenuated by Lck protein expression level.