bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTORC2 in Thymic Epithelial Cells Controls Thymopoiesis and T Cell Development
Authors: Wang Hong-Xia , Cheng Joyce S. , Chu Shuai , Qiu Yu-Rong , Zhong Xiao-Ping 
Published: May 2016

Abstract
Thymic epithelial cells (TECs) play important roles in T cell generation. Mechanisms that control TEC development and function are still not well defined. The mammalian or mechanistic target of rapamycin complex (mTORC)2 signals to regulate cell survival, nutrient uptake, and metabolism. We report in the present study that mice with TEC-specific ablation of Rictor, a critical and unique adaptor molecule in mTORC2, display thymic atrophy, which accompanies decreased TEC numbers in the medulla. Moreover, generation of multiple T cell lineages, including conventional TCRαβ T cells, regulatory T cells, invariant NKT cells, and TCRγδ T cells, was reduced in TEC-specific Rictor-deficient mice. Our data demonstrate that mTORC2 in TECs is important for normal thymopoiesis and efficient T cell generation.
Ly49C Impairs NK Cell Memory in Mouse Cytomegalovirus Infection
Authors: Forbes Catherine A. , Scalzo Anthony A. , Degli-Esposti Mariapia A. , Coudert Jerome D. 
Published: May 2016

Abstract
NK cells possess inhibitory receptors that are responsible for self-MHC class I recognition; beyond their inhibitory function, accumulating evidence indicates that such receptors confer NK cell functional competence through an unclear process termed “licensing.” Ly49C is the main self-specific inhibitory Ly49 receptor in H-2b C57BL/6 (B6) mice. We used B6 Ly49C-transgenic and B6 β2 microglobulin (β2m)-knockout Ly49C-transgenic mice to investigate the impact of licensing through this inhibitory receptor in precursor and mature NK cells. We found that self-specific inhibitory receptors affected NK cell precursor survival and proliferation at particular developmental stages in an MHC class I–dependent manner. The presence of Ly49C impacted the NK cell repertoire in a β2m-dependent manner, with reduced Ly49A+, Ly49G2+, and Ly49D+ subsets, an increased DNAM-1+ subset, and higher NKG2D expression. Licensed NK cells displayed a skewed distribution of the maturation stages, which was characterized by differential CD27 and CD11b expression, toward the mature phenotypes. We found that Ly49C-mediated licensing induced a split effect on NK cell functions, with increased cytokine-production capabilities following engagement of various activating receptors while cytotoxicity remained unchanged. Analysis of licensed NK cell functions in vivo, in a system of mouse CMV infection, indicated that licensing did not play a major role in the NK cell antiviral response during acute infection, but it strongly impaired the generation and/or persistence of memory NK cells. This study unravels multifaceted effects of licensing on NK cell populations and their functions.
Human Xenobiotic Nuclear Receptor PXR AugmentsMycobacterium tuberculosisSurvival
Authors: Bhagyaraj Ella , Nanduri Ravikanth , Saini Ankita , Dkhar Hedwin Kitdorlang , Ahuja Nancy , Chandra Vemika , Mahajan Sahil , Kalra Rashi , Tiwari Drishti , Sharma Charu , Janmeja Ashok Kumar , Gupta Pawan 
Published: May 2016

AbstractMycobacterium tuberculosis can evade host defense processes, thereby ensuring its survival and pathogenesis. In this study, we investigated the role of nuclear receptor, pregnane X receptor (PXR), in M. tuberculosis infection in human monocyte–derived macrophages. In this study, we demonstrate that PXR augments M. tuberculosis survival inside the host macrophages by promoting the foamy macrophage formation and abrogating phagolysosomal fusion, inflammation, and apoptosis. Additionally, M. tuberculosis cell wall lipids, particularly mycolic acids, crosstalk with human PXR (hPXR) by interacting with its promiscuous ligand binding domain. To confirm our in vitro findings and to avoid the reported species barrier in PXR function, we adopted an in vivo mouse model expressing hPXR, wherein expression of hPXR in mice promotes M. tuberculosis survival. Therefore, pharmacological intervention and designing antagonists to hPXR may prove to be a promising adjunct therapy for tuberculosis.
Cutting Edge: A Cullin-5–TRAF6 Interaction Promotes TRAF6 Polyubiquitination and Lipopolysaccharide Signaling
Authors: Zhu Ziyan , Wang Lili , Hao Rui , Zhao Bo , Sun Lei , Ye Richard D. 
Published: May 2016

Abstract
TNFR-associated factor (TRAF)6 integrates signals from multiple cell surface receptors for the activation of NF-κB. However, the mechanism underlying LPS-induced TRAF6 signaling remains unclear. We report that cullin-5 (Cul-5), a cullin family scaffold protein, binds to TRAF6 and promotes TRAF6 polyubiquitination at Lys63 in response to LPS stimulation. A direct interaction between the C-terminal domain of Cul-5 and the TRAF-C domain of TRAF6 facilitates polyubiquitination of TRAF6. Hemizygous Cul-5 knockout is associated with improved survival of mice following LPS challenge and significant delays in the phosphorylation of p65/RelA, ERK, JNK, and p38 MAPKs in LPS-stimulated macrophages, along with a marked decrease in NF-κB activation. These findings identify Cul-5 as a signaling component that connects an LPS-activated TLR4-MyD88 complex to TRAF6 for efficient activation of NF-κB.
The Ron Receptor Tyrosine Kinase Regulates Macrophage Heterogeneity and Plays a Protective Role in Diet-Induced Obesity, Atherosclerosis, and Hepatosteatosis
Authors: Yu Shan , Allen Joselyn N. , Dey Adwitia , Zhang Limin , Balandaram Gayathri , Kennett Mary J. , Xia Mingcan , Xiong Na , Peters Jeffrey M. , Patterson Andrew , Hankey-Giblin Pamela A. 
Published: May 2016

Abstract
Obesity is a chronic inflammatory disease mediated in large part by the activation of inflammatory macrophages. This chronic inflammation underlies a whole host of diseases including atherosclerosis, hepatic steatosis, insulin resistance, type 2 diabetes, and cancer, among others. Macrophages are generally classified as either inflammatory or alternatively activated. Some tissue-resident macrophages are derived from yolk sac erythromyeloid progenitors and fetal liver progenitors that seed tissues during embryogenesis and have the ability to repopulate through local proliferation. These macrophages tend to be anti-inflammatory in nature and are generally involved in tissue remodeling, repair, and homeostasis. Alternatively, during chronic inflammation induced by obesity, bone marrow monocyte-derived macrophages are recruited to inflamed tissues, where they produce proinflammatory cytokines and exacerbate inflammation. The extent to which these two populations of macrophages are plastic in their phenotype remains controversial. We have demonstrated previously that the Ron receptor tyrosine kinase is expressed on tissue-resident macrophages, where it limits inflammatory macrophage activation and promotes a repair phenotype. In this study, we demonstrate that Ron is expressed in a subpopulation of macrophages during chronic inflammation induced by obesity that exhibit a repair phenotype as determined by the expression of arginase 1. In addition, we demonstrate that the Ron receptor plays a protective role in the progression of diet-induced obesity, hepatosteatosis, and atherosclerosis. These results suggest that altering macrophage heterogeneity in vivo could have the potential to alleviate obesity-associated diseases.
Multispacecraft observations and modeling of the 22/23 June 2015 geomagnetic storm
Authors: Reiff P. H. , Daou A. G. , Sazykin S. Y. , Nakamura R. , Hairston M. R. , Coffey V. , Chandler M. O. , Anderson B. J. , Russell C. T. , Welling D. , Fuselier S. A. , Genestreti K. J. 
Published: May 2016

AbstractThe magnetic storm of 22–23 June 2015 was one of the largest in the current solar cycle. We present in situ observations from the Magnetospheric Multiscale Mission (MMS) and the Van Allen Probes (VAP) in the magnetotail, field‐aligned currents from AMPERE (Active Magnetosphere and Planetary Electrodynamics Response), and ionospheric flow data from Defense Meteorological Satellite Program (DMSP). Our real‐time space weather alert system sent out a “red alert,” correctly predicting Kp indices greater than 8. We show strong outflow of ionospheric oxygen, dipolarizations in the MMS magnetometer data, and dropouts in the particle fluxes seen by the MMS Fast Plasma Instrument suite. At ionospheric altitudes, the AMPERE data show highly variable currents exceeding 20 MA. We present numerical simulations with the Block Adaptive Tree‐Solarwind ‐ Roe ‐ Upwind Scheme (BATS‐R‐US) global magnetohydrodynamic model linked with the Rice Convection Model. The model predicted the magnitude of the dipolarizations, and varying polar cap convection patterns, which were confirmed by DMSP measurements.
Distinct impact of different types of aerosols on surface solar radiation in China
Authors: Yang Xin , Zhao Chuanfeng , Zhou Lijing , Wang Yang , Liu Xiaohong 
Published: May 2016

AbstractObservations of surface direct solar radiation (DSR) and visibility, particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5), together with the aerosol optical thickness (AOT) taken from Moderate‐Resolution Imaging Spectroradiometer and Multiangle Imaging Spectroradiometer, were investigated to gain insight into the impact of aerosol pollution on surface solar radiation in China. The surface DSR decreased during 2004–2014 compared with 1993~2003 over eastern China, but no clear reduction was observed in remote regions with cleaner air. Significant correlations of visibility, PM2.5, and regionally averaged AOT with the surface DSR over eastern China indicate that aerosol pollution greatly affects the energy available at the surface. The net loss of surface solar radiation also reduces the surface ground temperature over eastern China. However, the slope of the linear variation of the radiation with respect to atmospheric visibility is distinctly different at different stations, implying that the main aerosol type varies regionally. The largest slope value occurs at Zhengzhou and indicates that the aerosol absorption in central China is the highest, and lower slope values suggest relatively weakly absorbing types of aerosols at other locations. The spatial distribution of the linear slopes agrees well with the geographical distribution of the absorbing aerosols derived from the Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observations and Ozone Monitoring Instrument over China. The regional correlation between a larger slope value and higher absorbance properties of aerosols indicates that the net effects of aerosols on the surface solar energy and corresponding climatic effects are dependent on both aerosol amount and optical properties.
Characterization of group II chaperonins from an acidothermophilic archaeon Picrophilus torridus
Authors: Yamamoto Yohei Y. , Tsuchida Kanako , Noguchi Keiichi , Ogawa Naoki , Sekiguchi Hiroshi , Sasaki Yuji C. , Yohda Masafumi 
Published: May 2016

Chaperonins are a type of molecular chaperone that assist in the folding of proteins. Group II chaperonins play an important role in the proteostasis in the cytosol of archaea and eukarya. In this study, we expressed, purified, and characterized group II chaperonins from an acidothermophilic archaeon Picrophilus torridus. Two genes exist for group II chaperonins, and both of the gene products assemble to form double‐ring complexes similar to other archaeal group II chaperonins. One of the Picrophilus chaperonins, PtoCPNα, was able to refold denatured GFP at 50 °C. As expected, PtoCPNα exhibited an ATP‐dependent conformational change that is observed by the change in fluorescence and diffracted X‐ray tracking (DXT). In contrast, PtoCPNα lost its protein folding ability at moderate temperatures, becoming unable to interact with unfolded proteins. At lower temperatures, the release rate of the captured GFP from PtoCPNα was accelerated, and the affinity of denatured protein to PtoCPNα was weakened at the lower temperatures. Unexpectedly, in the DXT experiment, the fine motions were enhanced at the lower temperatures. Taken together, the results suggest that the fine tilting motions of the apical domain might correlate with the affinity of group II chaperonins for denatured proteins.
Equilibrium and Kinetic Behaviors of Cationic Dye Decolorization Using Poly (AN‐co‐Py)/ZrO2 Novel Nanopolymeric Composites
Authors: El‐Kady M. F. , El‐Aassar M. R. , El Batrawy Omnia A. , Ibrahim Mahmoud S. , Hassan H. Shokry , Fakhry Hala 
Published: May 2016

AbstractA novel nanopolymeric composite powdered material was prepared by physical immobilization of the sol‐gel prepared zirconia nanoparticles (ZrO2NPs) into poly (acrylonitrile‐ co‐pyrrole) (poly (AN‐co‐py)) copolymer. The prepared copolymer composite was characterized using scanning electron microscope (SEM) and Fourier Transfer infrared spectrophotometer (FT‐IR). SEM images investigated its homogeneous spherical morphological structure with an average diameter of 60 nm. The potential of this nanopolymeric composite material to remove a basic dye (Basic Red 46) was evaluated in a batch process. The improvement in material dosage, solution pH, and temperature has positive impact on the dye decolonization process. The maximum dye decolonization was 87.7% that recorded using 0.5 g from the composite matrix within 150 min. The kinetic data analysis indicated that the dye adsorption is a second‐order process. The results indicated that the prepared nanopolymeric composite could be an alternative for more costly adsorbents used for dye removal.
Helix Nucleation by the Smallest Known α‐Helix in Water
Authors: Hoang Huy N. , Driver Russell W. , Beyer Renée L. , Hill Timothy A. , D. de Araujo Aline , Plisson Fabien , Harrison Rosemary S. , Goedecke Lena , Shepherd Nicholas E. , Fairlie David P. 
Published: May 2016

AbstractCyclic pentapeptides (e.g. Ac‐(cyclo‐1,5)‐[KAXAD]‐NH2; X=Ala, 1; Arg, 2) in water adopt one α‐helical turn defined by three hydrogen bonds. NMR structure analysis reveals a slight distortion from α‐helicity at the C‐terminal aspartate caused by torsional restraints imposed by the K(i)–D(i+4) lactam bridge. To investigate this effect on helix nucleation, the more water‐soluble 2 was appended to N‐, C‐, or both termini of a palindromic peptide ARAARAARA (≤5 % helicity), resulting in 67, 92, or 100 % relative α‐helicity, as calculated from CD spectra. From the C‐terminus of peptides, 2 can nucleate at least six α‐helical turns. From the N‐terminus, imperfect alignment of the Asp5 backbone amide in 2 reduces helix nucleation, but is corrected by a second unit of 2 separated by 0–9 residues from the first. These cyclic peptides are extremely versatile helix nucleators that can be placed anywhere in 5–25 residue peptides, which correspond to most helix lengths in protein–protein interactions.
Modification of Wide‐Band‐Gap Oxide Semiconductors with Cobalt Hydroxide Nanoclusters for Visible‐Light Water Oxidation
Authors: Maeda Kazuhiko , Ishimaki Koki , Tokunaga Yuki , Lu Daling , Eguchi Miharu 
Published: May 2016

AbstractCobalt‐based compounds, such as cobalt(II) hydroxide, are known to be good catalysts for water oxidation. Herein, we report that such cobalt species can also activate wide‐band‐gap semiconductors towards visible‐light water oxidation. Rutile TiO2 powder, a well‐known wide‐band‐gap semiconductor, was capable of harvesting visible light with wavelengths of up to 850 nm, and thus catalyzed water oxidation to produce molecular oxygen, when decorated with cobalt(II) hydroxide nanoclusters. To the best of our knowledge, this system constitutes the first example that a particulate photocatalytic material that is capable of water oxidation upon excitation by visible light can also operate at such long wavelengths, even when it is based on earth‐abundant elements only.
Janus‐Cube Octasilsesquioxane: Facile Synthesis and Structure Elucidation
Authors: Oguri Naoki , Egawa Yasunobu , Takeda Nobuhiro , Unno Masafumi 
Published: May 2016

AbstractA perfect “Janus‐cube” octasilsesquioxane, a nanometer‐scale Janus particle with two different types of substituents, was synthesized through the cross‐coupling of a “half‐cube” cyclic sodium siloxanolate with another half‐cube cyclic fluorosiloxane. The structure was confirmed by X‐ray crystallography to be a Janus cube. The overall synthesis is simple and does not require drastic separation methods compared with previous methods. The synthesis of the Janus cube demonstrates a novel siloxane bond‐forming reaction involving the coupling a silanol salt and fluorosilane. The reaction is mild, does not result in acid generation, and could be applied to the construction of other novel siloxane compounds.
Neuronal differentiation in the developing human spinal ganglia
Authors: Vukojevic Katarina , Filipovic Natalija , Tica Sedlar Ivana , Restovic Ivana , Bocina Ivana , Pintaric Irena , Saraga‐Babic Mirna 
Published: May 2016

ABSTRACTThe spatiotemporal developmental pattern of the neural crest cells differentiation toward the first appearance of the neuronal subtypes was investigated in developing human spinal ganglia (SG) between the fifth and tenth developmental week using immunohistochemistry and immunofluorescence methods. First neurofilament‐200‐ (NF200, likely myelinated mechanoreceptors) and isolectin‐B4‐positive neurons (likely unmyelinated nociceptors) appeared already in the 5/6th developmental week and their number subsequently increased during the progression of development. Proportion of NF200‐positive cells was higher in the ventral parts of the SG than in the dorsal parts, particularly during the 5/6th and 9/10th developmental weeks (Mann–Whitney, P = 0.040 and P = 0.003). NF200 and IB4 colocalized during the whole investigated period. calcitonin gene‐related peptide (CGRP; nociceptive responses), vanilloid receptor‐1 (VR1; polymodal nociceptors), and calretinin (calcium signaling) cell immunoreactivity first appeared in the sixth week and eighth week, respectively, especially in the dorsal parts of the SG. VR1 and CGRP colocalized with NF00 during the whole investigated period. Our results indicate the high potential of early differentiated neuronal cells, which slightly decreased with the progression of SG differentiation. On the contrary, the number of neuronal subtypes displayed increasing differentiation at later developmental stage. The great diversity of phenotypic expression found in the SG neurons is the result of a wide variety of influences, occurring at different stages of development in a large potential repertory of these neurons. Understanding the pathway of neural differentiation in the human, SG could be important for the studies dealing with the process of regeneration of damaged spinal nerves or during the repair of pathological changes within the affected ganglia. Anat Rec, 299:1060–1072, 2016. © 2016 Wiley Periodicals, Inc.
Bayesian model selection in logistic regression for the detection of adverse drug reactions
Authors: Marbac Matthieu , Tubert‐Bitter Pascale , Sedki Mohammed 
Published: May 2016

Spontaneous adverse event reports have a high potential for detecting adverse drug reactions. However, due to their dimension, the analysis of such databases requires statistical methods. In this context, disproportionality measures can be used. Their main idea is to project the data onto contingency tables in order to measure the strength of associations between drugs and adverse events. However, due to the data projection, these methods are sensitive to the problem of coprescriptions and masking effects. Recently, logistic regressions have been used with a Lasso type penalty to perform the detection of associations between drugs and adverse events. On different examples, this approach limits the drawbacks of the disproportionality methods, but the choice of the penalty value is open to criticism while it strongly influences the results. In this paper, we propose to use a logistic regression whose sparsity is viewed as a model selection challenge. Since the model space is huge, a Metropolis–Hastings algorithm carries out the model selection by maximizing the BIC criterion. Thus, we avoid the calibration of penalty or threshold. During our application on the French pharmacovigilance database, the proposed method is compared to well‐established approaches on a reference dataset, and obtains better rates of positive and negative controls. However, many signals (i.e., specific drug–event associations) are not detected by the proposed method. So, we conclude that this method should be used in parallel to existing measures in pharmacovigilance.Code implementing the proposed method is available at the following url: https://github.com/masedki/MHTrajectoryR.
High‐resolution, hybrid optical trapping methods, and their application to nucleic acid processing proteins
Authors: Chemla Yann R. 
Published: May 2016

ABSTRACTOptical tweezers have become a powerful tool to investigate nucleic‐acid processing proteins at the single‐molecule level. Recent advances in this technique have now enabled measurements resolving the smallest units of molecular motion, on the scale of a single base pair of DNA. In parallel, new instrumentation combining optical traps with other functionalities have been developed, incorporating mechanical manipulation along orthogonal directions or fluorescence imaging capabilities. Here, we review these technical advances, their capabilities, and limitations, focusing on benchmark studies of protein‐nucleic acid interactions they have enabled. We highlight recent work that combines several of these advances together and its application to nucleic‐acid processing enzymes. Finally, we discuss future prospects for these exciting developments. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 704–714, 2016.
An open‐source platform for using gamification and social learning methodologies in engineering education: Design and experience
Authors: Sousa‐Vieira María Estrella , López‐Ardao Jose Carlos , Fernández‐Veiga Manuel , Rodríguez‐Pérez Miguel , Herrería‐Alonso Sergio 
Published: May 2016

ABSTRACTIt is commonly accepted that contemporary cohorts of students witness and experience the benefits of information technologies in their learning processes. The so‐called “digital natives” acquire, as a consequence of their early exposure to these technologies, different patterns of work, distinct attention conducts, new learning preferences and, generally, better skills for learning and working within rich online social contexts. So, it seems reasonable that the traditional education systems evolve and shape their practice to leverage those new patterns. Despite the fact that online social networks (osns) are widely recognized as a powerful vector for adding a new social dimension to the learning management systems (lmss), osns do not fully integrate the specific features of the learning process yet and traditional lmss do not exploit the advantages of an active social environment for reinforcing the learning experience. In this paper, we report the design, implementation, and use of a software platform (SocialWire) that leverages on the basic capabilities of an osn and extends the functionality toward its use in very general learning environments. We argue that this approach, together with gamification elements, is helpful in increasing the students’ motivation, besides improving the learning experience and performance. This software system has been in use for 3 years in different subject areas in our university. Our outcomes and the feedback provided both by teachers and students support the introduction of social features, gamification elements, and informal processes into the traditional teaching practices. © 2016 Wiley Periodicals, Inc. Comput Appl Eng Educ 24:813–826, 2016; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21746