bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nck Binds to the T Cell Antigen Receptor Using Its SH3.1 and SH2 Domains in a Cooperative Manner, Promoting TCR Functioning
Authors: Paensuwan Pussadee , Hartl Frederike A. , Yousefi O. Sascha , Ngoenkam Jatuporn , Wipa Piyamaporn , Beck-Garcia Esmeralda , Dopfer Elaine P. , Khamsri Boonruang , Sanguansermsri Donruedee , Minguet Susana , Schamel Wolfgang W. , Pongcharoen Sutatip 
Published: November 2015

Abstract
Ligand binding to the TCR causes a conformational change at the CD3 subunits to expose the CD3ε cytoplasmic proline-rich sequence (PRS). It was suggested that the PRS is important for TCR signaling and T cell activation. It has been shown that the purified, recombinant SH3.1 domain of the adaptor molecule noncatalytic region of tyrosine kinase (Nck) can bind to the exposed PRS of CD3ε, but the molecular mechanism of how full-length Nck binds to the TCR in cells has not been investigated so far. Using the in situ proximity ligation assay and copurifications, we show that the binding of Nck to the TCR requires partial phosphorylation of CD3ε, as it is based on two cooperating interactions. First, the SH3.1(Nck) domain has to bind to the nonphosphorylated and exposed PRS, that is, the first ITAM tyrosine has to be in the unphosphorylated state. Second, the SH2(Nck) domain has to bind to the second ITAM tyrosine in the phosphorylated state. Likewise, mutations of the SH3.1 and SH2 domains in Nck1 resulted in the loss of Nck1 binding to the TCR. Furthermore, expression of an SH3.1-mutated Nck impaired TCR signaling and T cell activation. Our data suggest that the exact pattern of CD3ε phosphorylation is critical for TCR functioning.
The Expression of BAFF Is Controlled by IRF Transcription Factors
Authors: Sjöstrand Maria , Johansson Alina , Aqrawi Lara , Olsson Tomas , Wahren-Herlenius Marie , Espinosa Alexander 
Published: November 2015

Abstract
Patients with systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are typically characterized by the presence of autoantibodies and an IFN-signature. The strength of the IFN-signature positively correlates with disease severity, suggesting that type I IFNs are active players in these diseases. BAFF is a cytokine critical for development and proper selection of B cells, and the targeting of BAFF has emerged as a successful treatment strategy of SLE. Previous reports have suggested that BAFF expression is directly induced by type I IFNs, but the precise mechanism for this remains unknown. In this article, we demonstrate that BAFF is a bona fide ISG and that IFN regulatory factors (IRFs) control the expression of BAFF. We identify IRF1 and IRF2 as positive regulators of BAFF transcription and IRF4 and IRF8 as potent repressors; in addition, we have mapped the precise binding site for these factors in the BAFF promoter. IFN-β injections induced BAFF expression mainly in neutrophils and monocytes, and BAFF expression in neutrophils from pSS patients strongly correlated with the strength of the IFN-signature. In summary, we show that BAFF expression is directly induced by type I IFNs via IRF1 and IRF2, whereas IRF4 and IRF8 are negative regulators of BAFF expression. These data suggest that type I IFN blockade in SLE and pSS patients will lead to downregulation of BAFF and a consequential reduction of autoreactive B cell clones and autoantibodies.
Nonclassical CD4+CD49b+ Regulatory T Cells as a Better Alternative to Conventional CD4+CD25+ T Cells To Dampen Arthritis Severity
Authors: Vicente Rita , Quentin Julie , Mausset-Bonnefont Anne-Laure , Chuchana Paul , Martire Delphine , Cren Maïlys , Jorgensen Christian , Louis-Plence Pascale 
Published: November 2015

Abstract
Promising immunotherapeutic strategies are emerging to restore tolerance in autoimmune diseases by triggering an increase in the number and/or the function of endogenous regulatory T (Treg) cells, which actively control pathological immune responses. Evidence suggests a remarkable heterogeneity in peripheral Treg cells that warrants their better characterization in terms of phenotype and suppressive function, to determine which subset may be optimally suitable for a given clinical situation. We found that repetitive injections of immature dendritic cells expanded Foxp3-negative CD49b+ Treg cells that displayed an effector memory phenotype. These expanded Treg cells were isolated ex vivo for transcriptome analysis and found to contain multiple transcripts of the canonical Treg signature shared mainly by CD25+ but also by other subphenotypes. We characterized the CD49b+ Treg cell phenotype, underscoring its similarities with the CD25+ Treg cell phenotype and highlighting some differential expression patterns for several markers, including lymphocyte activation gene 3, KLRG1, CD103, ICOS, CTLA-4, and granzyme B. Comparison of the CD25+ and CD49b+ Treg cells' suppressive mechanisms, in vitro and in vivo, revealed the latter's potent suppressive activity, which was partly dependent on IL-10 secretion. Altogether, our results strongly suggest that expression of several canonical Treg cell markers and suppressive function could be Foxp3 independent, and underscore the therapeutic potential of IL-10–secreting CD49b+ Treg cells in arthritis.
The IL-12 Response of Primary Human Dendritic Cells and Monocytes to Toxoplasma gondii Is Stimulated by Phagocytosis of Live Parasites Rather Than Host Cell Invasion
Authors: Tosh Kevin W. , Mittereder Lara , Bonne-Annee Sandra , Hieny Sara , Nutman Thomas B. , Singer Steven M. , Sher Alan , Jankovic Dragana 
Published: November 2015

Abstract
As a major natural host for Toxoplasma gondii, the mouse is widely used for the study of the immune response to this medically important protozoan parasite. However, murine innate recognition of toxoplasma depends on the interaction of parasite profilin with TLR11 and TLR12, two receptors that are functionally absent in humans. This raises the question of how human cells detect and respond to T. gondii. In this study, we show that primary monocytes and dendritic cells from peripheral blood of healthy donors produce IL-12 and other proinflammatory cytokines when exposed to toxoplasma tachyzoites. Cell fractionation studies determined that IL-12 and TNF-α secretion is limited to CD16+ monocytes and the CD1c+ subset of dendritic cells. In direct contrast to their murine counterparts, human myeloid cells fail to respond to soluble tachyzoite extracts and instead require contact with live parasites. Importantly, we found that tachyzoite phagocytosis, but not host cell invasion, is required for cytokine induction. Together these findings identify CD16+ monocytes and CD1c+ dendritic cells as the major myeloid subsets in human blood-producing innate cytokines in response to T. gondii and demonstrate an unappreciated requirement for phagocytosis of live parasites in that process. This form of pathogen sensing is distinct from that used by mice, possibly reflecting a direct involvement of rodents and not humans in the parasite life cycle.
TRPV4 Mechanosensitive Ion Channel Regulates Lipopolysaccharide-Stimulated Macrophage Phagocytosis
Authors: Scheraga Rachel G. , Abraham Susamma , Niese Kathryn A. , Southern Brian D. , Grove Lisa M. , Hite R. Duncan , McDonald Christine , Hamilton Thomas A. , Olman Mitchell A. 
Published: November 2015

Abstract
Macrophage phagocytosis of particles and pathogens is an essential aspect of innate host defense. Phagocytic function requires cytoskeletal rearrangements that depend on the interaction between macrophage surface receptors, particulates/pathogens, and the extracellular matrix. In the present study we determine the role of a mechanosensitive ion channel, transient receptor potential vanilloid 4 (TRPV4), in integrating the LPS and matrix stiffness signals to control macrophage phenotypic change for host defense and resolution from lung injury. We demonstrate that active TRPV4 mediates LPS-stimulated murine macrophage phagocytosis of nonopsonized particles (Escherichia coli) in vitro and opsonized particles (IgG-coated latex beads) in vitro and in vivo in intact mice. Intriguingly, matrix stiffness in the range seen in inflamed or fibrotic lung is required to sensitize the TRPV4 channel to mediate the LPS-induced increment in macrophage phagocytosis. Furthermore, TRPV4 is required for the LPS induction of anti-inflammatory/proresolution cytokines. These findings suggest that signaling through TRPV4, triggered by changes in extracellular matrix stiffness, cooperates with LPS-induced signals to mediate macrophage phagocytic function and lung injury resolution. These mechanisms are likely to be important in regulating macrophage function in the context of pulmonary infection and fibrosis.
A cGAS-Independent STING/IRF7 Pathway Mediates the Immunogenicity of DNA Vaccines
Authors: Suschak John J. , Wang Shixia , Fitzgerald Katherine A. , Lu Shan 
Published: November 2015

Abstract
It has been known since the discovery of DNA vaccines &gt;20 y ago that DNA vaccines can function as adjuvants. Our recent study reported the involvement of Aim2 as the sensor of DNA vaccines in eliciting Ag-specific Ab responses. Our findings indicated the presence of previously unrecognized innate immune response pathways in addition to the TLR9 pathway, which is mainly activated by the CpG motifs of DNA vaccines. Our data further demonstrated the requirement of type I IFN in DNA vaccine–induced immune responses via the Aim2 pathway, but the exact downstream molecular mechanism was not characterized. In the present study, we investigated the roles of the putative DNA sensor cyclic GMP–AMP synthase (cGas), as well as the downstream IFN regulatory factors (IRF) 3 and 7 in type I IFN induction and Ag-specific immune responses elicited by DNA vaccination. Our results showed that DNA vaccine–induced, Irf7-dependent signaling, as part of the Sting pathway, was critical for generation of both innate cytokine signaling and Ag-specific B and T cell responses. In contrast, Irf3 was not as critical as expected in this pathway and, more surprisingly, immune responses elicited by DNA vaccines were not cGas-dependent in vivo. Data from this study provide more details on the innate immune mechanisms involved in DNA vaccination and further enrich our understanding on the potential utility of DNA vaccines in generating Ag-specific immune responses.
Regulatory T Cell Induction and Retention in the Lungs Drives Suppression of Detrimental Type 2 Th Cells During Pulmonary Cryptococcal Infection
Authors: Wiesner Darin L. , Smith Kyle D. , Kotov Dmitri I. , Nielsen Judith N. , Bohjanen Paul R. , Nielsen Kirsten 
Published: November 2015

Abstract
Lethal disease caused by the fungus Cryptococcus neoformans is a consequence of the combined failure to control pulmonary fungal replication and immunopathology caused by induced type 2 Th2 cell responses in animal models. In order to gain insights into immune regulatory networks, we examined the role of regulatory T (Treg) cells in suppression of Th2 cells using a mouse model of experimental cryptococcosis. Upon pulmonary infection with Cryptococcus, Treg cells accumulated in the lung parenchyma independently of priming in the draining lymph node. Using peptide–MHC class II molecules to identify Cryptococcus-specific Treg cells combined with genetic fate-mapping, we noted that a majority of the Treg cells found in the lungs were induced during the infection. Additionally, we found that Treg cells used the transcription factor, IFN regulatory factor 4, to dampen harmful Th2 cell responses, as well as mediate chemokine retention of Treg cells in the lungs. Taken together, induction and IFN regulatory factor 4–dependent localization of Treg cells in the lungs allow Treg cells to suppress the deleterious effects of Th2 cells during cryptococcal infection.
Importation of Good Governance at Local Self-government Body in Bangladesh
Authors: Islam Fakhrul , Haque Md. Amdadul 
Published: November 2015

The principle of good governance is difficult and controversial. Governance opens new space which provides a concept that allows us to discuss the role of government in coping with public issues and the contribution that other players may make. It opens one’s mind to the possibility that groups in society other than government. Good governance is responsive to the present and future needs of society. Strengthening local governance can be ensured through the importation of the component of good governance at the local level. This paper intent to examine spaces where principles of good governance are required to apply to ensure better service delivery system at Union Parishad. This paper has been followed by social survey method. The data collection technique of this study has covered quantitative technique. Union Parishad as a local self government body ensuring community participations, people can approach and communicates clearly to their representatives and regularly issuing its progress report to the people for their transparency. Besides, dealing with convicted corruption was found most effective in manner.
Oude rechtskeuzes: de Erfrechtverordening en het overgangsrecht
Authors: Knot J.G. 
Published: November 2015

Oude rechtskeuzes: de Erfrechtverordening en het overgangsrecht
De Erfrechtverordening is van toepassing op grensoverschrijdende nalatenschappen die op of na 17 augustus 2015 openvallen. De verordening staat het toe ten aanzien van het toepasselijke erfrecht een rechtskeuze uit te brengen. De vraag rijst echter hoe volgens de verordening moet worden omgegaan met een reeds vóór 17 augustus 2015 uitgebrachte rechtskeuze. Deze overgangsrechtelijke vraag is met name in Nederland van belang, omdat de rechtskeuzemogelijkheden hier te lande voorheen ruimer waren dan onder de verordening. Daar staat dan weer tegenover dat de oude Nederlandse rechtskeuze alleen ten aanzien van de vererving van de nalatenschap gold en niet ten aanzien van de afwikkeling. In deze bijdrage wordt bezien welke oude Nederlandse rechtskeuzes onder de verordening geldig (kunnen) zijn en wat precies de werkingsomvang van deze oude rechtskeuzes is.
The Basics of Least Cost Analysis for Archaeological Applications
Authors: White Devin Alan 
Published: November 2015

AbstractLeast Cost Analysis (LCA) is a geospatially focused quantitative approach that can help archaeologists better understand how people may have moved across a landscape. At its core is the assumption that humans make decisions about movement as fully rational actors with complete knowledge of the landscape, attempting to minimize the cost of that movement as they travel from one location to another. LCA is most often used to construct a small number of hypothetical routes between locations of interest and, when used effectively, can even lead to the creation of entire transportation networks. Desktop GIS software packages, both commercial and open source, make running LCA relatively straightforward, but that does not necessarily mean that the output is informative or accurate. The following tutorial is designed to expose the reader to the foundational steps required to complete an LCA workflow, along with the scientific rationale behind each step and how to avoid potential pitfalls that one might run into along the way. Relevant literature is cited throughout the tutorial in order to provide context for the technical methods that underpin available tools, to suggest various ways that LCA can be used to solve archaeological problems, and to show the art of the possible.
BasicHPLCTheory and Definitions: Retention, Thermodynamics, Selectivity, Zone Spreading, Kinetics, and Resolution
Authors: Fornstedt Torgny , Forssén Patrik , Westerlund Douglas 
Published: November 2015

AbstractThis chapter covers the basic aspects of liquid chromatography such as retention models, kinetics, band broadening, the plate height concept, and the dependence of separation performance on flow rate. Together, this will form a basis to understand how to predict and improve separation performance and resolution for different types ofHPLCsystems. We conclude the chapter with today's trends in liquid chromatography and explain how these trends are linked to the basic aspects covered earlier.
BasicLCMethod Development and Optimization
Authors: Samanidou Victoria F. 
Published: November 2015

AbstractChromatography is the main part of separation science that has been established over a century ago and since then it has been catering to the demands of many scientific areas, such as biological, pharmaceutical, food, forensic, environmental, and so on. High‐pressure liquid chromatography (HPLC) is one of the most reliable analytical technologies in any analytical laboratory. It is, beyond any doubt, the most powerful weapon in an analyst's arsenal and the most useful tool toward any analytical challenge, no matter what the sample matrix is or how complicated it appears to be.Analytes are separated as they are distributed between two phases, the mobile phase and the stationary phase. It may sound an easy task but an analyst knows that this is not true at all. Getting well‐resolved peaks within a rational time span is the ultimate goal. The whole procedure is called HPLC method development, and undoubtedly, it is a complicated process. The physicochemical properties of the analytes to be separated are the driving force of this procedure.In this chapter, the principal factors that have to be investigated duringLCmethod development and optimization are discussed.
Recent Advances in Column Technology
Authors: Shalliker Ross Andrew , Kocic Danijela 
Published: November 2015

Abstract

Over the past half century, there has been a substantial development in the modern chromatography column. Particle sizes have decreased from 10 to now sub‐2 μm, and with it the number of theoretical plates has increased to about 200 000 per meter on fully porous particles, and 250 000 plates per meter for core–shell particles.
Despite this change, the number of plates used per separation has not changed that much, since shorter columns must be used when packed with the smaller particles because a great deal more pressure is required to drive mobile phase through the column. One significant change, however, is that separations have got faster as a result of the decrease in particle size.

Nevertheless, over time, one fundamental problem still exists; packed beds are heterogeneous, and this is a source of performance loss. To overcome the consequences of packing heterogeneity, a new column technology has been developed, which is called active flow technology (
AFT
). This technology minimizes the significance of the wall effect and provides much greater separation efficiency, while enabling faster separations, especially when coupled to MS detection. This chapter highlights the causes of column bed heterogeneity and presents active flow technology columns, illustrating briefly some of the new directions that the development of this column technology can take.
Reversed Phase Liquid Chromatography
Authors: García‐Alvarez‐Coque Maria C. , Baeza‐Baeza Juan J. , Ramis‐Ramos Guillermo 
Published: November 2015

AbstractReversed phase liquid chromatography (RPLC) is a mode of high‐performance liquid chromatography (HPLC) that employs a nonpolar stationary phase (most frequently a hydrocarbon chain chemically bonded to porous silica particles) and a polar mobile phase constituted by water and at least a water‐miscible organic solvent, which performs as a modifier.RPLCis a mature technique, employed in science and technology by chemists, biochemists, and pharmacists for analysis and purification. Applications cover environmental control, food, clinical, pharmaceutical, and industrial analyses, drug and chemical manufacturing (at both quality control and preparative scales), biomedical studies, and measurement of physicochemical properties. The development ofRPLChas been based primarily on empirical observations. The diversity of retention mechanisms has received considerable attention, sometimes with conflicting results. This reflects the difficulty in understanding the underlying principles. In this chapter, the theoretical background and technical traits ofRPLCare outlined. The factors that contribute to the separation are described, together with the main approaches proposed to understand the observed behaviors. The advantages and limitations of using either isocratic or gradient elution are discussed. A picture of the retention behavior at the molecular level, including a description of the dewetting effect of highly aqueous mobile phases, is also given. The trends in the current evolution of the technique are commented upon. The overview contains over 100 references.
Normal‐Phase and Polar Organic Solvents Chromatography
Authors: Younes Ahmed A. , Galea Charlene , Mangelings Debby , Vander Heyden Y. 
Published: November 2015

Abstract

This chapter starts with a brief overview of chromatography and focuses on liquid chromatography, particularly
NPLC
and
POSC
. Retention mechanisms both for polarity‐based separations seen in
NPLC
and
POSC
and for charge and size‐based separations are explained. The second part of the chapter focuses on different stationary and mobile phases that can be combined together to give a chromatographic system with an acceptable separation and required selectivity. Factors that should be kept in mind when switching from one stationary or mobile phase to another are highlighted and examples that facilitate understanding are used.
Chiral Separation of Some Classes of Pesticides by
HPLC
Method
Authors: Ali Imran , Hussain Iqbal , Sanagi Mohd Marsin , Aboul‐Enein Hassan Y. 
Published: November 2015

Abstract

About 28% of pesticides are chiral, and simple analyses of pesticides are creating confusion due to the fact that one of the enantiomers is toxic to pests, while the other is a burden for the environment. Moreover, different toxicities of the enantiomers confuse farmers when they measure the dose lethal for pests. Therefore, chiral analysis is an important issue for chemical, agrochemical, and chemical industries. Attempts have been made to describe state‐of‐the‐art methods of chiral analysis of pesticides by
HPLC
using various types of chiral columns, eluents, and other
HPLC
conditions along with the chiral recognition mechanisms involved in chiral separation using different chiral stationary phases (
CSPs
).
Gas Chromatography: Theory and Thermodynamics, and Selectivity
Authors: Spangler Glenn E. 
Published: November 2015

AbstractAfter a brief historical introduction to gas chromatography, the principles of operation are explained. Following a brief discussion of the earlier retention time and plate theories, a more advanced continuum theory is systematically developed with liberal cross‐referencing to the open scientific literature. The chromatogram for methanol injected into a Rtx‐5 (5% diphenyl/95% dimethyl polysiloxane) column coupled to an injector and detector is modeled and nomenclature established for its description. Finally, issues related to sensitivity, resolution, and temperature programming are discussed.
Current Use of Gas Chromatography and Applications
Authors: Vetter Walter 
Published: November 2015

AbstractOver the past 60 years, gas chromatography (GC) has been developed into the most powerful separation technique for volatile compounds. This chapter describes milestones in this success story, classic and recent developments in modern instrumentation ofGC, current applications and trends as well as future perspectives, and how they fit together. Sections discuss novel stationary phases, comprehensiveGC,GCdetectors, the referencing ofGCdata as well as instrumental miniaturization, applications in the analysis of fatty acids, flavor compounds, pollutants and drugs as well as special sections on direct enantiomer separations using modified cyclodextrins, inverse gas chromatography, and microgas chromatographic separations.