bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoplasmic Reticulum Stress–Induced IRE1α Activation Mediates Cross-Talk of GSK-3β and XBP-1 To Regulate Inflammatory Cytokine Production
Authors: Kim Sena , Joe Yeonsoo , Kim Hyo Jeong , Kim You-Sun , Jeong Sun Oh , Pae Hyun-Ock , Ryter Stefan W. , Surh Young-Joon , Chung Hun Taeg 
Published: March 2015

Abstract
IL-1β and TNF-α are important proinflammatory cytokines that respond to mutated self-antigens of tissue damage and exogenous pathogens. The endoplasmic reticulum (ER) stress and unfolded protein responses are related to the induction of proinflammatory cytokines. However, the detailed molecular pathways by which ER stress mediates cytokine gene expression have not been investigated. In this study, we found that ER stress–induced inositol-requiring enzyme (IRE)1α activation differentially regulates proinflammatory cytokine gene expression via activation of glycogen synthase kinase (GSK)-3β and X-box binding protein (XBP)-1. Surprisingly, IL-1β gene expression was modulated by IRE1α-mediated GSK-3β activation, but not by XBP-1. However, IRE1α-mediated XBP-1 splicing regulated TNF-α gene expression. SB216763, a GSK-3 inhibitor, selectively inhibited IL-1β gene expression, whereas the IRE1α RNase inhibitor STF083010 suppressed only TNF-α production. Additionally, inhibition of GSK-3β greatly increased IRE1α-dependent XBP-1 splicing. Our results identify an unsuspected differential role of downstream mediators GSK-3β and XBP-1 in ER stress–induced IRE1α activation that regulates cytokine production through signaling cross-talk. These results have important implications in the regulation of inflammatory pathways during ER stress, and they suggest novel therapeutic targets for diseases in which meta-inflammation plays a key role.
Antibodies Generated against Streptococci Protect in a Mouse Model of Disseminated Aspergillosis
Authors: Wharton Rebekah E. , Stefanov Emily K. , King R. Glenn , Kearney John F. 
Published: March 2015

Abstract
Invasive aspergillosis (IA) resulting from infection by Aspergillus fumigatus is a leading cause of death in immunosuppressed populations. There are limited therapeutic options for this disease and currently no vaccine. There is evidence that some anti–A. fumigatus mAbs can provide protection against IA. However, vaccine development has been impeded by a paucity of immunological targets on this organism demonstrated to provide protective responses. Sialylated oligosaccharide epitopes found on a variety of pathogens, including fungi and group B streptococci (GBS), are thought to be major virulence factors of these organisms facilitating pathogen attachment to host cells and modulating complement activation and phagocytosis. Because some of these oligosaccharide structures are conserved across kingdoms, we screened a panel of mAbs raised against GBS serotypes for reactivity to A. fumigatus. This approach revealed that SMB19, a GBSIb type–specific mAb, reacts with A. fumigatus conidia and hyphae. The presence of this Ab in mice, as a result of passive or active immunization, or by enforced expression of the SMB19 H chain as a transgene, results in significant protection in both i.v. and airway-induced models of IA. This study demonstrates that some Abs generated against bacterial polysaccharides engage fungal pathogens and promote their clearance in vivo and thus provide rationale of alternative strategies for the development of vaccines or therapeutic mAbs against these organisms.
Regulatory T Cells Require TCR Signaling for Their Suppressive Function
Authors: Schmidt Amanda M. , Lu Wen , Sindhava Vishal J. , Huang Yanping , Burkhardt Janis K. , Yang Enjun , Riese Matthew J. , Maltzman Jonathan S. , Jordan Martha S. , Kambayashi Taku 
Published: March 2015

Abstract
Regulatory T cells (Tregs) are a subset of CD4+ T cells that maintain immune tolerance in part by their ability to inhibit the proliferation of conventional CD4+ T cells (Tconvs). The role of the TCR and the downstream signaling pathways required for this suppressive function of Tregs are not fully understood. To yield insight into how TCR-mediated signals influence Treg suppressive function, we assessed the ability of Tregs with altered TCR-mediated signaling capacity to inhibit Tconv proliferation. Mature Tregs deficient in Src homology 2 domain containing leukocyte protein of 76 kDa (SLP-76), an adaptor protein that nucleates the proximal signaling complex downstream of the TCR, were unable to inhibit Tconv proliferation, suggesting that TCR signaling is required for Treg suppressive function. Moreover, Tregs with defective phospholipase C γ (PLCγ) activation due to a Y145F mutation of SLP-76 were also defective in their suppressive function. Conversely, enhancement of diacylglycerol-mediated signaling downstream of PLCγ by genetic ablation of a negative regulator of diacylglycerol kinase ζ increased the suppressive ability of Tregs. Because SLP-76 is also important for integrin activation and signaling, we tested the role of integrin activation in Treg-mediated suppression. Tregs lacking the adaptor proteins adhesion and degranulation promoting adapter protein or CT10 regulator of kinase/CT10 regulator of kinase–like, which are required for TCR-mediated integrin activation, inhibited Tconv proliferation to a similar extent as wild-type Tregs. Together, these data suggest that TCR-mediated PLCγ activation, but not integrin activation, is required for Tregs to inhibit Tconv proliferation.
Microtubule Nucleation in Mouse Bone Marrow–Derived Mast Cells Is Regulated by the Concerted Action of GIT1/βPIX Proteins and Calcium
Authors: Sulimenko Vadym , Hájková Zuzana , Černohorská Markéta , Sulimenko Tetyana , Sládková Vladimíra , Dráberová Lubica , Vinopal Stanislav , Dráberová Eduarda , Dráber Pavel 
Published: March 2015

Abstract
Ag-mediated activation of mast cells initiates signaling events leading to Ca2+ response, release of allergic mediators from cytoplasmic granules, and synthesis of cytokines and chemokines. Although microtubule rearrangement during activation has been described, the molecular mechanisms that control their remodeling are largely unknown. Microtubule nucleation is mediated by complexes that are formed by γ-tubulin and γ-tubulin complex proteins. In this study, we report that, in bone marrow–derived mast cells (BMMCs), γ-tubulin interacts with p21-activated kinase interacting exchange factor β (βPIX) and G protein–coupled receptor kinase-interacting protein (GIT)1. Microtubule regrowth experiments showed that the depletion of βPIX in BMMCs stimulated microtubule nucleation, whereas depletion of GIT1 led to the inhibition of nucleation compared with control cells. Phenotypic rescue experiments confirmed that βPIX and GIT1 represent negative and positive regulators of microtubule nucleation in BMMCs, respectively. Live-cell imaging disclosed that both proteins are associated with centrosomes. Immunoprecipitation and pull-down experiments revealed that an enhanced level of free cytosolic Ca2+ affects γ-tubulin properties and stimulates the association of GIT1 and γ-tubulin complex proteins with γ-tubulin. Microtubule nucleation also was affected by Ca2+ level. Moreover, in activated BMMCs, γ-tubulin formed complexes with tyrosine-phosphorylated GIT1. Further experiments showed that GIT1 and βPIX are involved in the regulation of such important physiological processes as Ag-induced chemotaxis and degranulation. Our study provides for the first time, to our knowledge, a possible mechanism for the concerted action of tyrosine kinases, GIT1/βPIX proteins, and Ca2+ in the propagation of signals leading to the regulation of microtubule nucleation in activated mast cells.
Cutting Edge: Antimalarial Drugs Inhibit IFN-β Production through Blockade of Cyclic GMP-AMP Synthase–DNA Interaction
Authors: An Jie , Woodward Joshua J. , Sasaki Tomikazu , Minie Mark , Elkon Keith B. 
Published: March 2015

AbstractType I IFN is strongly implicated in the pathogenesis of systemic autoimmune diseases, such as lupus, and rare monogenic IFNopathies, including Aicardi–Goutières syndrome. Recently, a new DNA-activated pathway involving the enzyme cyclic GMP-AMP synthase (cGAS) was described and potentially linked to Aicardi–Goutières syndrome. To identify drugs that could potentially inhibit cGAS activity, we performed in silico screening of drug libraries. By computational analysis, we identified several antimalarial drugs (AMDs) that were predicted to interact with the cGAS/dsDNA complex. Our studies validated that several AMDs were effective inhibitors of IFN-β production and that they functioned by inhibiting dsDNA stimulation of cGAS. Because AMDs have been widely used in human diseases and have an excellent safety profile, our findings suggest new therapeutic strategies for the treatment of severe debilitating diseases associated with type I IFNs due to cGAS activation.
The characteristics of HIV and AIDS patients with deep vein thrombosis at Dr. George Mukhari Academic Hospital
Authors: Govender Indiran , Mabuza Honey L. , Ogunbanjo Gboyega A 
Published: March 2015

Background: Deep vein thrombosis (DVT) is 10 times more prevalent in HIV and AIDS patients than in the general population and is more common in patients with severe immune suppression (CD4 < 200 cells/mL). Opportunistic infections render HIV and AIDS patients susceptible to a hypercoaguable state, including lower protein S levels. Aim and setting: To present the profile of HIV and AIDS patients who developed DVT in the primary care wards of Dr. George Mukhari Academic Hospital (DGMAH), Garankuwa. Methods: Cross-sectional study of clinical records of admitted HIV and AIDS patients without DVT to the primary care wards, DGMAH, from 01 February 2010 to 31 January 2011. Results: Two hundred and twenty-nine patients were admitted and 17 (7.4%) developed DVT. Of those that developed DVT, eight (47%) had infection with tuberculosis (TB), four (24%) had pneumonia and four (24%) had gastroenteritis. The risk of developing DVT was 8/94 (8.5%) in those with TB, 4/53 (7.5%) in those with gastroenteritis and 4/75 (5.3%) in those with pneumonia. The mean duration of stay was 14.1 days in those with DVT versus 4.0 days in those without. Conclusion: HIV (and AIDS) is a hypercoaguable state and the risk of DVT is relatively high in patients with opportunistic infections. HIV and AIDS patients who are admitted to hospital with opportunistic infections may benefit from anti-thrombotic prophylaxis and further studies are needed to evaluate this.
Lawyer of defendant and his role in the criminal process from the viewpoint of the European Convention on Human Rights and the Albanian criminal procedural legislation
Authors: Skenderaj Klodjan , Mëngjesi Sokol 
Published: March 2015

A guarantee for real ensuring of defendant’s rights is the qualified legal assistance by the side of the lawyer, chosen or assigned by the proceeding body. Providing legal protection to defendants was an important achievement in the long and difficult efforts to democratize the criminal proceedings. It was initially achieved in developed countries which promulgated the fundamental rights and freedoms and on this basis the major laws of activity of justice’s bodies were enforced. The role of lawyer in the criminal proceeding gradually increased and became an important factor in the fight against violations of law and injustice. The lawyer became a respected procedural figure, standing in front of prosecution, as the opposing party able to develop a cross-examination and to influence in a fair solution of case. However in practice, it is not rare the violation of rights of defendants by proceeding organs. So, it is right to make this question: What will be done with their rights and how will they be protected? In practice there were different opinions in terms of guaranteeing the rights of these defendants and how far the rights of lawyers of the defendants are extended. This is the reason why this paper will bring in attention the position, procedural guarantees of lawyers, the actions that can take and the exercise of their main rights in defending the interest of defendant, taking into account the main phases of criminal proceedings. Special attention will be devoted to case law of European Court of Human Rights (ECHR) in terms of guaranteeing the rights of defendants, the orientations of the Albanian Constitutional Court and that of Supreme Court. At the end, this paper will reach in some conclusions through which proposals and amendments will be made to the code of criminal procedure, starting from the principle that the rights and procedural guarantees of defendants should be guaranteed at the maximum, because it’s the only way to achieve the highest degree of democratization of the criminal proceedings.
Women’s Roles and Participation in Rituals in the Maintenance of Cultural Identity: A Study of the Malaysian Iyers
Authors: Vijaya Sankar Lokasundari 
Published: March 2015

AbstractThis paper examines the roles and rituals practiced by Malaysian Iyer women. The Iyers are a small community of Tamil Brahmins who live and work mainly in the Klang Valley. As an Indian diasporic community, who moved to Malaysia from the early 1900s, they have been slowly shifting from Tamil to English and Malay. They are upwardly mobile and place great emphasis on education but at the same time, value their traditions and culture. Data was derived from interactions between women and men from the Malaysian Iyer community together with personal observations made during visits to their homes, weddings and prayer sessions. This data was studied to obtain insights into cultural elements that ruled their discourse. The findings show that for this diasporic community that was slowly losing its language, ethnic identity can still be found in their cultural practices. Women were seen as keepers of tradition and customs that are important to the community. They followed certain cultural and traditional practices in their homes: practiced vegetarianism while cooking and serving food in their homes, followed taboos regarding food preparation, maintained patriarchal practices especially in religious practices and lived in extended families which usually included paternal grandparents. Malaysian Iyer women are seen to continue with the traditional roles given to women of the community.
Gatekeeping in the Coverage of Interethnic Conflicts: An Analysis of Mainstream and Alternative Newspapers in Malaysia
Authors: Lai Fong Yang , Ahmad Ishak Sidin 
Published: March 2015

Abstract
Ethnicity, religion and related issues have always proved to be a difficult topic for reporting in multicultural societies. This study examined the gatekeeping process undertaken by Malaysian newspapers in reporting interethnic conflicts. The gatekeeping theory was employed as the theoretical framework. Interviews with editors from the mainstream and alternative newspapers found that gatekeeping took place at the individual, routine, and organizational as well as institutional levels. Significantly, two newspapers owned by pro-government political parties – Utusan by UMNO and The Star by MCA – claimed that ownership had an impact on their gatekeeping decision. It was found that political reason was the primary external factor influencing the gatekeeping of the newspapers in their coverage of interethnic conflicts. This study indicates that journalists/editors shape a reality that reflects the political, economic and ideological boundaries within which they work. More importantly, gatekeeping was found to reflect a struggle between dominant social norms and efforts for change.
Critical Analysis Of Multiphernia and Identity in Two Selected Malaysian Novels
Authors: Farahmandian Hamid 
Published: March 2015

AbstractThe texts that have been selected to analyse multiphrenia and identity issues areGreen is the Color byLloyd Fernando andMr.Tang’s Girlsby Shirley Lim. In this paper, I discuss how post-modern characteristics of self-creation define the protoganist’s identity while in the second novel, I explore the influence of patriarchal society on the shaping of the protagonist’s identity. The patriarchal society for which the protagonist’s father is an example is considered the ‘other’ as seen in Burke and Stets’ (2009) ‘the nature of the individual depends upon the society in which he or she lives’.
The electrical structure of the central Pacific upper mantle constrained by the NoMelt experiment
Authors: Sarafian Emily , Evans Rob. L. , Collins John A. , Elsenbeck Jimmy , Gaetani Glenn A. , Gaherty James B. , Hirth Greg , Lizarralde Daniel 
Published: March 2015

AbstractThe NoMelt experiment imaged the mantle beneath 70 Ma Pacific seafloor with the aim of understanding the transition from the lithosphere to the underlying convecting asthenosphere. Seafloor magnetotelluric data from four stations were analyzed using 2‐D regularized inverse modeling. The preferred electrical model for the region contains an 80 km thick resistive (>103 Ωm) lithosphere with a less resistive (∼50 Ωm) underlying asthenosphere. The preferred model is isotropic and lacks a highly conductive (≤10 Ωm) layer under the resistive lithosphere that would be indicative of partial melt. We first examine temperature profiles that are consistent with the observed conductivity profile. Our profile is consistent with a mantle adiabat ranging from 0.3 to 0.5°C/km. A choice of the higher adiabatic gradient means that the observed conductivity can be explained solely by temperature. In contrast, a 0.3°C/km adiabat requires an additional mechanism to explain the observed conductivity profile. Of the plausible mechanisms, H2O, in the form of hydrogen dissolved in olivine, is the most likely explanation for this additional conductivity. Our profile is consistent with a mostly dry lithosphere to 80 km depth, with bulk H2O contents increasing to between 25 and 400 ppm by weight in the asthenosphere with specific values dependent on the choice of laboratory data set of hydrous olivine conductivity and the value of mantle oxygen fugacity. The estimated H2O contents support the theory that the rheological lithosphere is a result of dehydration during melting at a mid‐ocean ridge with the asthenosphere remaining partially hydrated and weakened as a result.
Electromagnetic fluctuations of the whistler‐cyclotron and firehose instabilities in a Maxwellian and Tsallis‐kappa‐like plasma
Authors: Viñas Adolfo F. , Moya Pablo S. , Navarro Roberto E. , Valdivia J. Alejandro , Araneda Jaime A. , Muñoz Víctor 
Published: March 2015

AbstractObserved electron velocity distributions in the Earth's magnetosphere and the solar wind exhibit a variety of nonthermal features which deviate from thermal equilibrium, for example, in the form of temperature anisotropies, suprathermal tail extensions, and field‐aligned beams. The state close to thermal equilibrium and its departure from it provides a source for spontaneous emissions of electromagnetic fluctuations, such as the whistler. Here we present a comparative analysis of the electron whistler‐cyclotron and firehose fluctuations based upon anisotropic plasma modeled with Maxwellian and Tsallis‐kappa‐like particle distributions, to explain the correspondence relationship of the magnetic fluctuations as a function of the electron temperature and thermal anisotropy in the solar wind and magnetosphere plasmas. The analysis presented here considers correlation theory of the fluctuation‐dissipation theorem and the dispersion relation of transverse fluctuations, with wave vectors parallel to the uniform background magnetic field, in a finite temperature anisotropic thermal bi‐Maxwellian and nonthermal Tsallis‐kappa‐like magnetized electron‐proton plasma. Dispersion analysis and stability thresholds are derived for these thermal and nonthermal distributions using plasma and field parameters relevant to the solar wind and magnetosphere environments. Our results indicate that there is an enhancement of the fluctuations level in the case of nonthermal distributions due to the effective higher temperature and the excess of suprathermal particles. These results suggest that a comparison of the electromagnetic fluctuations due to thermal and nonthermal distributions provides a diagnostic signature by which inferences about the nature of the particle velocity distribution function can be ascertained without in situ particle measurements.
Influences on the positioning of mantle plumes following supercontinent formation
Authors: Heron Philip J. , Lowman Julian P. , Stein Claudia 
Published: March 2015

AbstractSeveral mantle convection studies analyzing the effects of supercontinent formation and dispersal show that the genesis of subcontinental plumes results from the formation of subduction zones at the edges of the supercontinent rather than from the effect of continental thermal insulation or thermochemical piles. However, the influence of subduction zone location on the position of subcontinental plumes has received little attention. This study analyzes 2‐D and 3‐D numerical models of supercontinent formation (in an isochemical mantle) to assess the role of subduction and mantle viscosity contrast in the generation of subcontinental mantle plumes. We find that once a critical supercontinent width is reached, plumes do not form under the center of a supercontinent. In studies featuring a low viscosity lower mantle, the surface positions of the initial plumes (arriving within 90 Myr of supercontinent assembly) become locked beneath the continent at a distance 2000–3000 km from the continental margin. However, the broad downwellings in simulations that feature a high‐viscosity lower mantle trigger plumes at a greater distance from the continental margin subduction. For all mantle viscosity profiles, subcontinental plumes show dependence on the location of supercontinent margin subduction. As theories differ on the role of core‐mantle boundary chemical piles in plume formation, it is significant that our isochemical models show that the formation of subduction zones at the margins of a supercontinent has a profound effect on subcontinental mantle dynamics. Our results may help to explain what determined the eruption sites of past (and future) large igneous provinces.
Optical modeling of volcanic ash particles using ellipsoids
Authors: Merikallio Sini , Muñoz Olga , Sundström Anu‐Maija , Virtanen Timo H. , Horttanainen Matti , Leeuw Gerrit de , Nousiainen Timo 
Published: March 2015

AbstractThe single‐scattering properties of volcanic ash particles are modeled here by using ellipsoidal shapes. Ellipsoids are expected to improve the accuracy of the retrieval of aerosol properties using remote sensing techniques, which are currently often based on oversimplified assumptions of spherical ash particles. Measurements of the single‐scattering optical properties of ash particles from several volcanoes across the globe, including previously unpublished measurements from the Eyjafjallajökull and Puyehue volcanoes, are used to assess the performance of the ellipsoidal particle models. These comparisons between the measurements and the ellipsoidal particle model include consideration of the whole scattering matrix, as well as sensitivity studies on the point of view of the Advanced Along Track Scanning Radiometer (AATSR) instrument. AATSR, which flew on the ENVISAT satellite, offers two viewing directions but no information on polarization, so usually only the phase function is relevant for interpreting its measurements. As expected, ensembles of ellipsoids are able to reproduce the observed scattering matrix more faithfully than spheres. Performance of ellipsoid ensembles depends on the distribution of particle shapes, which we tried to optimize. No single specific shape distribution could be found that would perform superiorly in all situations, but all of the best‐fit ellipsoidal distributions, as well as the additionally tested equiprobable distribution, improved greatly over the performance of spheres. We conclude that an equiprobable shape distribution of ellipsoidal model particles is a relatively good, yet enticingly simple, approach for modeling volcanic ash single‐scattering optical properties.