bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection
Authors: Goodier Martin R. , Rodriguez-Galan Ana , Lusa Chiara , Nielsen Carolyn M. , Darboe Alansana , Moldoveanu Ana L. , White Matthew J. , Behrens Ron , Riley Eleanor M.
Published: May 2016

Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2–dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV−) individuals than in HCMV-seropositive (HCMV+) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV+ and HCMV− subjects. In addition to these IL-2–dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57− NK cells and was most evident in HCMV+ subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection.
Imatinib Triggers Phagolysosome Acidification and Antimicrobial Activity againstMycobacterium bovisBacille Calmette–Guérin in Glucocorticoid-Treated Human Macrophages
Authors: Steiger Julia , Stephan Alexander , Inkeles Megan S. , Realegeno Susan , Bruns Heiko , Kröll Philipp , de Castro Kroner Juliana , Sommer Andrea , Batinica Marina , Pitzler Lena , Kalscheuer Rainer , Hartmann Pia , Plum Georg , Stenger Steffen , Pellegrini Matteo , Brachvogel Bent , Modlin Robert L. , Fabri Mario
Published: May 2016

Glucocorticoids are extensively used to treat inflammatory diseases; however, their chronic intake increases the risk for mycobacterial infections. Meanwhile, the effects of glucocorticoids on innate host responses are incompletely understood. In this study, we investigated the direct effects of glucocorticoids on antimycobacterial host defense in primary human macrophages. We found that glucocorticoids triggered the expression of cathelicidin, an antimicrobial critical for antimycobacterial responses, independent of the intracellular vitamin D metabolism. Despite upregulating cathelicidin, glucocorticoids failed to promote macrophage antimycobacterial activity. Gene expression profiles of human macrophages treated with glucocorticoids and/or IFN-γ, which promotes induction of cathelicidin, as well as antimycobacterial activity, were investigated. Using weighted gene coexpression network analysis, we identified a module of highly connected genes that was strongly inversely correlated with glucocorticoid treatment and associated with IFN-γ stimulation. This module was linked to the biological functions autophagy, phagosome maturation, and lytic vacuole/lysosome, and contained the vacuolar H+-ATPase subunit a3, alias TCIRG1, a known antimycobacterial host defense gene, as a top hub gene. We next found that glucocorticoids, in contrast with IFN-γ, failed to trigger expression and phagolysosome recruitment of TCIRG1, as well as to promote lysosome acidification. Finally, we demonstrated that the tyrosine kinase inhibitor imatinib induces lysosome acidification and antimicrobial activity in glucocorticoid-treated macrophages without reversing the anti-inflammatory effects of glucocorticoids. Taken together, we provide evidence that the induction of cathelicidin by glucocorticoids is not sufficient for macrophage antimicrobial activity, and identify the vacuolar H+-ATPase as a potential target for host-directed therapy in the context of glucocorticoid therapy.
A Novel Role for TL1A/DR3 in Protection against Intestinal Injury and Infection
Authors: Jia Li-Guo , Bamias Giorgos , Arseneau Kristen O. , Burkly Linda C. , Wang Eddy C. Y. , Gruszka Dennis , Pizarro Theresa T. , Cominelli Fabio
Published: May 2016

TNF-like cytokine 1A (TL1A) is expressed on APCs and provides costimulatory signals to activated lymphocytes that bear its functional receptor, death receptor 3 (DR3). TL1A/DR3 signaling is involved in the pathogenesis of human and experimental inflammatory bowel disease. In the current study, we investigated the role of this cytokine/receptor pair in acute intestinal injury/repair pathways. We demonstrate that intact DR3 signaling protected mice from acute dextran sodium sulfate colitis because DR3−/− mice showed more severe mucosal inflammation and increased mortality. DR3−/− mice were compromised in their ability to maintain adequate numbers of CD4+CD25+Foxp3+ regulatory T cells in response to acute mucosal damage. This defect in immune regulation led to a nonspecific upregulation of effector proinflammatory pathways, which was most prominent for the Th17 immunophenotype. TL1A−/− mice were similarly more susceptible to dextran sodium sulfate colitis, although without mortality and with delayed kinetics compared with DR3−/− mice, and also displayed significantly reduced numbers of regulatory T cells. Infection of DR3−/− mice with Salmonella typhimurium was associated with defective microbial clearance and elevated bacterial load. Taken together, our findings indicate a novel protective role for the TL1A/DR3 axis in the regulation of mucosal homeostasis during acute intestinal injury/repair, which contrasts with its known pathogenic function during chronic intestinal inflammation.
Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential
Authors: Swaims-Kohlmeier Alison , Haaland Richard E. , Haddad Lisa B. , Sheth Anandi N. , Evans-Strickfaden Tammy , Lupo L. Davis , Cordes Sarah , Aguirre Alfredo J. , Lupoli Kathryn A. , Chen Cheng-Yen , Ofotukun Igho , Hart Clyde E. , Kohlmeier Jacob E.
Published: May 2016

The female genital tract (FGT) provides a means of entry to pathogens, including HIV, yet immune cell populations at this barrier between host and environment are not well defined. We initiated a study of healthy women to characterize resident T cell populations in the lower FGT from lavage and patient-matched peripheral blood to investigate potential mechanisms of HIV sexual transmission. Surprisingly, we observed FGT CD4 T cell populations were primarily CCR7hi, consistent with a central memory or recirculating memory T cell phenotype. In addition, roughly half of these CCR7hi CD4 T cells expressed CD69, consistent with resident memory T cells, whereas the remaining CCR7hi CD4 T cells lacked CD69 expression, consistent with recirculating memory CD4 T cells that traffic between peripheral tissues and lymphoid sites. HIV susceptibility markers CCR5 and CD38 were increased on FGT CCR7hi CD4 T cells compared with blood, yet migration to the lymphoid homing chemokines CCL19 and CCL21 was maintained. Infection with GFP-HIV showed that FGT CCR7hi memory CD4 T cells are susceptible HIV targets, and productive infection of CCR7hi memory T cells did not alter chemotaxis to CCL19 and CCL21. Variations of resident CCR7hi FGT CD4 T cell populations were detected during the luteal phase of the menstrual cycle, and longitudinal analysis showed the frequency of this population positively correlated to progesterone levels. These data provide evidence women may acquire HIV through local infection of migratory CCR7hi CD4 T cells, and progesterone levels predict opportunities for HIV to access these novel target cells.
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

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

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

Mycobacterium 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

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

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.
A general iterative solver for unbalanced inconsistent transportation problems
Authors: Carp Doina , Popa Constantin , Serban Cristina
Published: May 2016

The transportation problem, as a particular case of a linear programme, has probably the highest relative frequency with which appears in applications. At least in its classical formulation, it involves demands and supplies. When, for practical reasons, the total demand cannot satisfy the total supply, the problem becomes unbalanced and inconsistent, and must be reformulated as e.g. finding a least squares solution of an inconsistent system of linear inequalities. A general iterative solver for this class of problems has been proposed by S. P. Han in his 1980 original paper. The drawback of Han’s algorithm consists in the fact that it uses in each iteration the computation of the Moore-Penrose pseudoinverse numerical solution of a subsystem of the initial one, which for bigger dimensions can cause serious computational troubles. In order to overcome these difficulties we propose in this paper a general projection-based minimal norm solution approximant to be used within Han-type algorithms for approximating least squares solutions of inconsistent systems of linear inequalities. Numerical experiments and comparisons on some inconsistent transport model problems are presented.
A perceptual-behavioural approach with non-parametric experimental coefficient for urban parking business design
Authors: Ferrarese Moreno
Published: May 2016

Transportation science and integrated logistics of passengers in the cities provide a detailed study of the movements both on entry to the urban areas than within them. Parking lots are, very often, places of exchange between the motorized and the pedestrian or cycling mode, or between individual and collective motorized modes. As the modern urban civilization is known by its impetuous car parking expansion it becomes essential to design the parking lots bearing in mind the needs of those who will really use them and not referring to the political lobbies in the city administration. The study of parking lot in terms of business and financial design, planning and management after the construction needs is a more accurate determination of the experimental parameters, which enable choice of the model to minimize the uncertainty of the data that will define the revenues according to the Project Financing procedures.
Models of maritime safety for development of navigation support systems
Authors: Gucma Maciej
Published: May 2016

Navigation support systems are part of modern maritime transportation chain where larger and larger vessels are handled in ports. Support systems for sea navigation must meet certain criteria for access, integrity, accuracy and other factors. Modelling of safety criteria for technical creation of support systems like PNS (Pilot Navigation System) or LDS (Laser Docking System) consists of several stages both conceptual, and real time experimental. Even basic systems must be designed and developed in manner where assumed safety factors are met.
Studies and assessment of transport noise in Poznan
Authors: Orczyk Małgorzata , Tomaszewski Franciszek
Published: May 2016

In many cities in Poland, because of the lack of ring roads, the main traffic routes of state roads go through the cities affecting local and regional traffic. This causes high traffic and also many undesired effects for inhabitants such us environmental pollution with fumes, vibrations of buildings, high level of noise and increase of accidents. This article presents results of measurements of volume of traffic and noise level in selected traffic routes in Poznan. For the research the sections of roads and crossings that belong to state roads and important urban roads of Poznan were selected. The research was conducted according to recommendations included in the regulation of the Minister of the Environment of 16 June 2011 on requirements for conducting measurements of the levels of substances or energy in the environment by administrators of road, railway, tram line, airport or sea port. In most of the streets of Poznan, where measurements were made, registered equivalent sound levels exceed permissible levels defined in the regulation of the Ministry of the Environment about permissible noise levels in the environment. Equivalent sound levels registered at defined measurement points show values in scope between 53 and 78 dB.
Selection of the most adequate trip-modelling tool for integrated transport planning system
Authors: Sawicki Piotr , Kiciński Marcin , Fierek Szymon
Published: May 2016

This paper deals with the problem of selection the most suitable trip-modelling tool (TMT), which is a part of the more complex integrated transport planning system (ITPS) at the regional scale. Since an application of TMT is not autonomous and several different users exist the selection problem is not a trivial. In this paper, an original five-phase selection procedure is presented. The first phase consists in specifica¬tion of both, detailed expectations of all identified users and technical requirements of ITPS. Second phase deals with research on available TMT while a third one is concentrated on defining a comprehensive set of criteria. In this phase critical criteria as well as selection criteria are defined. First one is utilised to eliminate unacceptable TMTs in phase four and second one to evaluate and select most adequate TMT in phase five. In the paper an exemplary application of this procedure is presented. The authors have defined 2 critical criteria and a set of 19 selection criteria. The last one is divided into 3 main subsets, i.e. functional, technical and financial contexts of selection process. All the selection criteria are characterised by 43 sub-criteria and some of them are more detailed extended. Using this procedure 3 out of 6 alternative TMTs including Emme, Aimsun and Visum have been initially accepted and next evaluated. Finally, Visum has been selected and recommended for application into ITPS.
Research of lateral force of pipe conveyor belt’s vertical transport section
Authors: Wang Shuang , Guo Yong-Cun , Li De-Yong , Hu Kun
Published: May 2016

In order to release the lateral force of pipe conveyor belt in vertical transportation, the thesis had a study of the lateral force of the conveyor belt. By making use of Janssen Principles and fractal theory, based on reasonable simplification, the author established a mathematical model of the lateral force in vertical transportation, and with the research foundation of the pipe belt conveyor for underground transportation, through solution analysis, the author found out that the change of material diameter would lead to nonlinear variation of the lateral force of the conveyor belt. Under the circumstances of different material diameter, discrete element method was adopted to simulate the lateral force of the conveyor belt, thus working out the distribution curve chart of the lateral force. To verify the reliability of the theory, the author built an experimental platform for pipe conveyor belt in vertical transportation, and experimented with five groups of materials in different diameter, working out the strain of lateral force of the characteristic conveyor belt; by comparing the theoretical result, the simulation result and the experimental result, it showed that the solution to relieving lateral force through optimization selection of material diameter put forward in this thesis was reasonable and effective. It provides theoretical reference for the design of pipe belt conveyor.
Conflict-free trajectory planning based on the model predictive control theory
Authors: Yun-xiang Han , Xiao-qiong Huang
Published: May 2016

Model Predictive Control (MPC) is a model-based control method based on a receding horizon approach and online optimization. A key advantage of MPC is that it can accommodate constraints on the inputs and outputs. This paper proposes a max-plus general modeling framework adapted to the robust optimal control of air traffic flow in the airspace. It is shown that the problem can be posed as the control of queues with safety separation-dependent service rate. We extend MPC to a class of discrete-event system that can be described by models that are linear in the max-plus algebra with noise or modeling errors. Regarding the single aircraft as a batch, the relationships between input variables, state variables and output variable are established. We discuss some key properties of the system model and indicate how these properties can be used to analyze the behavior of air traffic flow. The model predictive control design problems are defined for this type of discrete event system to help prepare the airspace for various robust regulation needs and we give some extensions of the air traffic max-plus linear systems.
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

The 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

Observations 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.
Weakly Conjugated Hybrid Zinc Porphyrin Sensitizers for Solid‐State Dye‐Sensitized Solar Cells
Authors: Qin Peng , Sanghyun Paek , Dar M. Ibrahim , Rakstys Kasparas , ElBatal Hany , Al‐Muhtaseb Shaheen A. , Ludwig Christian , Nazeeruddin Mohammad Khaja
Published: May 2016

Molecularly engineered weakly conjugated hybrid porphyrin systems are presented as efficient sensitizers for solid‐state dye‐sensitized solar cells. By incorporating the quinolizino acridine and triazatruxene based unit as the secondary light‐harvester as well as electron‐donating group at the meso‐position of the porphyrin core, the power conversion efficiencies of 4.5% and 5.1% are demonstrated in the solid‐state devices containing 2,2′,7,7′‐tetrakis (N,N‐di‐p‐methoxyphenylamine)‐9,9′‐spiro bifluorene as hole transporting material. The photovoltaic performance of the triazatruxene donor based porphyrin sensitizer is better than that of the previously published porphyrin molecules exhibiting strongly conjugated push–pull structure. The effect of molecular structure on the optical and electrochemical properties, the dynamics of charge extraction, as well as the photovoltaic performance are systematically investigated, which offers a new design strategy for further refinement of porphyrin molecules.
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

A 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

Cyclic 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

Cobalt‐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

A 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

The 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.
MOLECULAR CHARACTERIZATION OF AUTOPHAGY‐RELATED GENE 5 FROM Spodoptera exigua AND EXPRESSION ANALYSIS UNDER VARIOUS STRESS CONDITIONS
Authors: Liu Kai‐Yu , Xia Yu‐Qian , Zhou Jing , Chen Zu‐Wen , Lu Dandan , Zhang Ning‐Zhao , Liu Xu‐Sheng , Ai Hui , Zhou Li‐Lin
Published: May 2016

Autophagy is not only involved in development, but also has been proved to attend immune response against invading pathogens. Autophagy protein 5 (ATG5) is an important autophagic protein, which plays a crucial role in autophagosome elongation. Although ATG5 has been well studied in mammal, yeast, and Drosophila, little is known about ATG5 in lepidopteran insects. We cloned putative SeAtg5 gene from Spodoptera exigua larvae by the rapid amplification of cDNA ends method, and its characteristics and the influences of multiple exogenous factors on its expression levels were then investigated. The results showed that the putative S. exigua SeATG5 protein is highly homologous to other insect ATG5 proteins, which has a conserved Pfm domain and multiple phosphorylation sites. Next, fluorescence microscope observation showed that mCherry‐SeATG5 was distributed in both nucleus and cytoplasm of Spodoptera litura Sl‐HP cells and partially co‐localized with BmATG6‐GFP, but it almost has no significant co‐localization with GFP‐HaATG8. Then, the Western blot analysis demonstrated that GFP‐SeATG5 conjugated with ATG12. Moreover, real‐time PCR revealed that its expression levels significantly increased at the initiation of pupation and the stage of adult. In addition, the expression levels of SeAtg5 can be enhanced by the starvation, UV radiation, and infection of baculovirus and bacterium. However, the expression levels of SeAtg5 decreased at 24 h post treatments in all these treatments except in starvation. These results suggested that SeATG5 might be involved in response of S. exigua under various stress conditions.
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.
A global × global test for testing associations between two large sets of variables
Authors: Chaturvedi Nimisha , de Menezes Renée X. , Goeman Jelle J.
Published: May 2016

In high‐dimensional omics studies where multiple molecular profiles are obtained for each set of patients, there is often interest in identifying complex multivariate associations, for example, copy number regulated expression levels in a certain pathway or in a genomic region. To detect such associations, we present a novel approach to test for association between two sets of variables. Our approach generalizes the global test, which tests for association between a group of covariates and a single univariate response, to allow high‐dimensional multivariate response. We apply the method to several simulated datasets as well as two publicly available datasets, where we compare the performance of multivariate global test (G2) with univariate global test. The method is implemented in R and will be available as a part of the globaltest package in R.
High‐resolution, hybrid optical trapping methods, and their application to nucleic acid processing proteins
Authors: Chemla Yann R.
Published: May 2016

Optical 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

It 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
Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis
Authors: Zheng Shanbo , Wang Rui , Zhang Yang , Pan Yunjian , Cheng Chao , Zheng Difan , Sun Yihua , Chen Haiquan
Published: May 2016

The aim of this present investigation was to evaluate the clinicopathologic characteristics, oncogenic drivers, and prognosis of former smokers with non‐small‐cell lung cancer (NSCLC), and to compare them with those of the current and never smokers. This investigation was a single‐institution retrospective study of 2289 NSCLC patients, who were classified as former, current, or never smokers. A collection was made of the clinicopathological characteristics, spectra of well‐identified driver genes and survival rates. The survival rates were compared using log‐rank test, and independent prognostic factors, identified using Cox regression analysis. Of 2289 NSCLC patients, 257 (11.2%) were former smokers; 868 (37.9%), current smokers; and 1164 (50.9%), never smokers. Compared with the current, the former were characterized by older age at diagnosis (64.3y vs. 59.9y; P < 0.001), earlier TNM stage (stage I, 47.9% vs. 39.5%; P = 0.017), fewer solid predominance in adenocarcinomas (16.2% vs. 29.5%; P = 0.005), and more EGFR mutation (33.2% vs. 20.7%; P < 0.001) but less KRAS mutation (6.7% vs. 11.9%, P = 0.041). No statistically significant survival differences were observed between the former and current. However, the light former smokers presented favorable overall survival when compared with the light current and heavy former or current (the light former vs. the heavy former, P = 0.028; the light former vs. the light current, P = 0.048; and the light former vs. the heavy current, P = 0.048). Our findings suggest that the former smokers with NSCLCs can have distinctive clinicopathologic characteristics, oncogenic drivers, and prognosis, and they, especially the light former, can benefit from smoking cessation.