bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncanonical Notch Signaling Modulates Cytokine Responses of Dendritic Cells to Inflammatory Stimuli
Authors: Gentle Madeleine E. , Rose Anna , Bugeon Laurence , Dallman Margaret J. 
Published: July 2012

Abstract
Dendritic cell (DC)-derived cytokines play a key role in specifying adaptive immune responses tailored to the type of pathogen encountered and the local tissue environment. However, little is known about how DCs perceive the local environment. We investigated whether endogenous Notch signaling could affect DC responses to pathogenic stimuli. We demonstrate that concurrent Notch and TLR stimulation results in a unique cytokine profile in mouse bone-marrow derived DCs characterized by enhanced IL-10 and IL-2, and reduced IL-12 expression compared with TLR ligation alone. Unexpectedly, modulation of cytokine production occurred through a noncanonical Notch signaling pathway, independent of γ-secretase activity. Modulation required de novo protein synthesis, and PI3K, JNK, and ERK activity were necessary for enhanced IL-2 expression, whereas modulation of IL-10 required only PI3K activity. Further, we show that this γ-secretase–independent Notch pathway can induce PI3K activity. In contrast, expression of the canonical Notch target gene Hes1 was suppressed in DCs stimulated with Notch and TLR ligands simultaneously. Thus, our data suggest that Notch acts as an endogenous signal that modulates cytokine expression of DCs through a noncanonical pathway and therefore has the potential to tailor the subsequent adaptive immune response in a tissue- and/or stage-dependent manner.
Endoplasmic Reticulum Stress Response Promotes Cytotoxic Phenotype of CD8αβ+ Intraepithelial Lymphocytes in a Mouse Model for Crohn’s Disease-like Ileitis
Authors: Chang Jung-Su , Ocvirk Soeren , Berger Emanuel , Kisling Sigrid , Binder Uli , Skerra Arne , Lee Amy S. , Haller Dirk 
Published: July 2012

Abstract
Endoplasmic reticulum (ER) unfolded protein responses (UPR) are implicated in the pathogenesis of inflammatory bowel disease. Cytotoxic CD8αβ+ intraepithelial lymphocytes (IEL) contribute to the development of Crohn’s disease-like ileitis in TNFΔARE/+ mice. In this study, we characterized the role of ER-UPR mechanisms in contributing to the disease-associated phenotype of cytotoxic IEL under conditions of chronic inflammation. Inflamed TNFΔARE/+ mice exhibited increased expression of Grp78, ATF6, ATF4, and spliced XBP1 in CD8αβ+ IEL but not in CD8αα+ IEL or in lamina propria lymphocytes. Chromatin immunoprecipitation analysis in CD8αβ+ T cells showed selective recruitment of ER-UPR transducers to the granzyme B gene promoter. Heterozygous Grp78−/+ mice exhibited an attenuated granzyme B-dependent cytotoxicity of CD8αβ+ T cells against intestinal epithelial cells, suggesting a critical activity of this ER-associated chaperone in maintaining a cytotoxic T cell phenotype. Granzyme B-deficient CD8αβ+ T cells showed a defect in IL-2–mediated proliferation in Grp78−/+ mice. Adoptively transferred Grp78−/+ CD8αβ+ T cells had a decreased frequency of accumulation in the intestine of RAG2−/− recipient mice. The tissue pathology in TNFΔARE/+ × Grp78−/+ mice was similar to TNFΔARE/+ mice, even though the cytotoxic effector functions of CD8αβ+ T cells were significantly reduced. In conclusion, ER stress-associated UPR mechanisms promote the development and maintenance of the pathogenic cytotoxic CD8αβ+ IEL phenotype in the mouse model of Crohn’s disease-like ileitis.
Cutting Edge: CTLA-4 on Effector T Cells Inhibits In Trans
Authors: Corse Emily , Allison James P. 
Published: July 2012

Abstract
CTLA-4 is thought to inhibit effector T cells both intrinsically, by competing with CD28 for B7 ligands, and extrinsically, through the action of regulatory T cells (Tregs). We studied in vivo responses of normal and CTLA-4–deficient Ag-specific murine effector CD4+ T cells. We directly demonstrate that effector T cell-restricted CTLA-4 inhibits T cell responses in a cell-extrinsic manner. Cotransfer experiments show that CTLA-4 on normal effector CD4+ T cells completely abrogates the dramatically increased expansion normally experienced by their CTLA-4–deficient counterparts. Neither the wild-type nor the CTLA-4–deficient T cells express the Treg transcription factor Foxp3 when transferred alone or together. Thus, cell-extrinsic inhibition of T cell responses by CTLA-4 is not limited to Tregs but is also a function of effector T cells.
The Adjuvant LT-K63 Can Restore Delayed Maturation of Follicular Dendritic Cells and Poor Persistence of Both Protein- and Polysaccharide-Specific Antibody-Secreting Cells in Neonatal Mice
Authors: Bjarnarson Stefania P. , Adarna Brenda C. , Benonisson Hreinn , Del Giudice Giuseppe , Jonsdottir Ingileif 
Published: July 2012

Abstract
Ab responses in early life are low and short-lived; therefore, induction of protective immunity requires repeated vaccinations. One of the major limitations in early-life immunity is delayed maturation of follicular dendritic cells (FDCs), which play a central role in mediating the germinal center (GC) reaction leading to production of Ab-secreting cells (AbSCs). We assessed whether a nontoxic mutant of Escherichia coli heat-labile enterotoxin (LT-K63) and CpG1826 as model adjuvants could accelerate FDC maturation and immune response in neonatal mice, using a pneumococcal polysaccharide of serotype 1 conjugated to tetanus toxoid (Pnc1-TT) as a model vaccine. In neonatal NMRI mice, a single dose of Pnc1-TT coadministered with LT-K63 enhanced Pnc1-TT–induced GC reaction. In contrast, CpG1826 had no effect. Accordingly, LT-K63, but not CpG1826, accelerated the maturation of FDC networks, detected by FDC-M2+ staining, characteristic for adult-like FDCs. This coincided with migration of MOMA-1+ macrophages into the GCs that can enhance GC reaction and B cell activation. The FDC-M2+ FDC networks colocalized with enhanced expression of TNF-α, which is critical for the maintenance of mature FDCs and is poorly expressed in neonates. The accelerated maturation of FDC networks correlated with increased frequency and prolonged persistence of polysaccharide- and protein-specific IgG+ AbSCs in spleen and bone marrow. Our data show for the first time, to our knowledge, that an adjuvant (LT-K63) can overcome delayed maturation of FDCs in neonates, enhance the GC reaction, and prolong the persistence of vaccine-specific AbSCs in the BM. These properties are attractive for parenteral vaccination in early life.
PROPHYLAXIS OF MALARIA
Authors: Schwartz Eli 
Published: July 2012

Malaria prevention in travelers to endemic areas remains dependent principally on chemoprophylaxis. Although malaria chemoprophylaxis refers to all malaria species, a distinction should be drawn between falciparum malaria prophylaxis and the prophylaxis of the relapsing malaria species (vivax & ovale). While the emergence of drug resistant strains, as well as the costs and adverse reactions to medications, complicate falciparum prophylaxis use, there are virtually no drugs available for vivax prophylaxis, beside of primaquine. Based on travelers malaria data, a revised recommendation for using chemoprophylaxis in low risk areas should be considered
Covering the Unit Sphere of Certain Banach Spaces by Sequences of Slices and Balls
Authors: Fonf Vladimir P. , Zanco Clemente 
Published: July 2012

AbstractWe prove that, given any covering of any infinite-dimensional Hilbert space H by countably many closed balls, some point exists in H which belongs to infinitely many balls. We do that by characterizing isomorphically polyhedral separable Banach spaces as those whose unit sphere admits a point-finite covering by the union of countably many slices of the unit ball.
Characterization of Autologous Mesenchymal Stem Cell-Derived Neural Progenitors as a Feasible Source of Stem Cells for Central Nervous System Applications in Multiple Sclerosis
Authors: Harris Violaine K. , Faroqui Raihan , Vyshkina Tamara , Sadiq Saud A. 
Published: June 2012

Abstract
Bone marrow mesenchymal stem cell-derived neural progenitors (MSC-NPs) are a potential therapeutic source of cells that have been shown to be efficacious in a preclinical model of multiple sclerosis (MS). To examine the feasibility of using MSC-NPs as an autologous source of cells to promote central nervous system (CNS) repair in MS, this study characterized human MSC-NPs from a panel of both MS and non-MS donors. Expanded MSCs showed similar characteristics in terms of growth and cell surface phenotype, regardless of the donor disease status. MSC-NPs derived from all MSCs showed a consistent pattern of gene expression changes that correlated with neural commitment and increased homogeneity. Furthermore, the reduced expression of mesodermal markers and reduced capacity for adipogenic or osteogenic differentiation in MSC-NPs compared with MSCs suggested that MSC-NPs have reduced potential of unwanted mesodermal differentiation upon CNS transplantation. The immunoregulatory function of MSC-NPs was similar to that of MSCs in their ability to suppress T-cell proliferation and to promote expansion of FoxP3-positive T regulatory cells in vitro. In addition, MSC-NPs promoted oligodendroglial differentiation from brain-derived neural stem cells that correlated with the secretion of bioactive factors. Our results provide a set of identity characteristics for autologous MSC-NPs and suggest that the in vitro immunoregulatory and trophic properties of these cells may have therapeutic value in the treatment of MS.
Concise Review: Tissue-Engineered Vascular Grafts for Cardiac Surgery: Past, Present, and Future
Authors: Kurobe Hirotsugu , Maxfield Mark W. , Breuer Christopher K. , Shinoka Toshiharu 
Published: June 2012

Abstract
In surgical repair for heart or vascular disease, it is often necessary to implant conduits or correct tissue defects. The most commonly used graft materials to date are (a) artificial grafts; (b) autologous tissues, such as pericardium and saphenous vein; (c) allografts; and (d) xenografts. However, none of these four options offer growth potential, and all are associated with varying levels of thrombogenicity and susceptibility to infection. The lack of growth potential of these four options is particularly important in pediatric cardiac surgery, where patients will often outgrow their vascular grafts and require additional operations. Thus, developing a material with sufficient durability and growth potential that will function as the child grows older will eliminate the need for reoperation and significantly reduce morbidity and mortality of some types of congenital heart defects. Vascular tissue engineering is a relatively new field that has undergone enormous growth over the last decade. The goal of vascular tissue engineering is to produce neovessels and neo-organ tissue from autologous cells using a biodegradable polymer as a scaffold. The most important advantage of tissue-engineered implants is that these tissues can grow, remodel, rebuild, and respond to injury. Once the seeded autologous cells have deposited an extracellular matrix and the original scaffold is biodegraded, the tissue resembles and behaves as native tissue. When tissue-engineered vascular grafts are eventually put to use in the clinical arena, the quality of life in patients after surgery will be drastically improved.
Increasing Donor Designation through Black Churches: Results of a Randomized Trial
Authors: Andrews Ann M. , Zhang Nanhua , Magee John C. , Chapman Remonia , Langford Aisha T. , Resnicow Ken 
Published: June 2012

Context African Americans are disproportionately represented among those awaiting a transplant, but many are reluctant to donate their organs. Objective To test the effectiveness of using lay health advisors to increase organ donation among church members. Design Churches were pair-matched by average estimated income and size and then randomized to 1 of 2 interventions: one addressing organ donation and the other addressing increasing consumption of fruits and vegetables. Setting Twenty-two African American churches in Southeast Michigan. Patients or Other Participants Church members were trained to serve as lay health advisors (called peer leaders). Interventions Peer leaders conducted organ donation discussions with church groups and showed a DVD created for this program that was tailored to African American churches. Main Outcome Measures The primary outcome was verified registration in the state's donor registry. Participants also completed pre/post questionnaires regarding their attitudes about organ donation. Results Once clustering, baseline value, and demographics were adjusted for, the intervention and comparison groups did not differ on any of the 3 attitude scales on the posttest. In logistic regression analysis, with baseline donation status, demographics, and church clustering controlled for, the odds of self-reported enrollment at 1-year posttest did not differ by condition (odds ratio, 1.23; 95% CI, 0.87–1.72). A total of 211 enrollments in the state registry from participating churches were verified. Of these, 163 were from intervention churches and 48 were from comparison churches. Conclusions Use of lay health advisors through black churches can increase minority enrollment in a donor registry even absent change in attitudes.
Gene Delivery Using Helper Virus‐Free HSV‐1 Amplicon Vectors
Authors: Laimbacher Andrea S. , Fraefel Cornel 
Published: July 2012

AbstractHerpes simplex virus type 1 (HSV‐1)‐based amplicon vectors contain only a very small percentage of the 152‐kbp viral genome. Consequently, replication and packaging of amplicons depend on helper functions that are provided either by replication‐defective mutants of HSV‐1 or by replication‐competent, but packaging‐defective, HSV‐1 genomes. Sets of cosmids that overlap and represent the entire HSV‐1 genome can form, via homologous recombination, circular replication‐competent viral genomes, which give rise to infectious virus progeny. However, if the DNA cleavage/packaging signals are deleted, reconstituted virus genomes are not packageable, but still provide all the helper functions required for the packaging of cotransfected amplicon DNA. The resulting stocks of packaged amplicon vectors are essentially free of contaminating helper virus. This unit describes the cotransfection of amplicon and cosmid or bacterial artificial chromosome (BAC) DNA into 2‐2 cells by cationic liposome‐mediated transfection and the harvesting of packaged vector particles. Support protocols provide methods for preparing cosmid and BAC DNA and determining the titers of amplicon stocks. Curr. Protoc. Neurosci. 60:4.14.1‐4.14.21. © 2012 by John Wiley & Sons, Inc.
Assays for Investigating deSUMOylation Enzymes
Authors: Madu Ikenna G. , Chen Yuan 
Published: July 2012

AbstractPost‐translational modifications by the SUMO (Small Ubiquitin‐like MOdifier) family of proteins are recently discovered essential regulatory mechanisms. All SUMO proteins are synthesized as larger precursors that are matured by SUMO‐specific proteases, known as SENPs, which remove several C‐terminal amino acids of SUMO to expose the Gly‐Gly motif. SENPs also remove SUMO modifications from target proteins, making this modification highly dynamic. At least six deSUMOylation enzymes, all of which are encoded by essential genes, have been identified in mammals. SENP1 has been shown to play an important role in the development of prostate cancer and in angiogenesis. This unit describes and discusses methods for characterizing the deSUMOylation enzymes. These assays enable the identification of inhibitors of these enzymes and investigation of their mechanism of inhibition in order to develop research tools and future therapeutics. Curr. Protoc. Mol. Biol. 99:10.30.1‐10.30.13. © 2012 by John Wiley & Sons, Inc.
Three‐Dimensional Second‐Harmonic Generation Imaging of Fibrillar Collagen in Biological Tissues
Authors: Xie Jiansong , Ferbas John , Juan Gloria 
Published: July 2012

AbstractMultiphoton‐induced second‐harmonic generation (SHG) has developed into a very powerful approach for in depth visualization of some biological structures with high specificity. In this unit, we describe the basic principles of three‐dimensional SHG microscopy. In addition, we illustrate how SHG imaging can be utilized to assess collagen fibrils in biological tissues. Some technical considerations are also addressed. Curr. Protoc. Cytom. 61:6.33.1‐6.33.11. © 2012 by John Wiley & Sons, Inc.
Full‐time workers with precarious employment face lower protection for receiving annual health check‐ups
Authors: Inoue Mariko , Tsurugano Shinobu , Nishikitani Mariko , Yano Eiji 
Published: July 2012

AbstractBackgroundPrecarious employment is one of the social determinants of health. In 2010, 34.4% of Japanese workers fell into this employment category. The purpose of our study was to assess whether the use of annual health check‐ups varied by worker contract type.MethodsUsing 2007 nationally representative survey data, we compared the annual health check‐up compliance of permanently employed full‐time workers versus that of precariously employed workers (hourly, dispatched, and fixed‐term workers).ResultsDispatched workers and hourly workers received health check‐ups less often compared with permanent workers. Hourly young male workers received health check‐ups five times less frequently than permanent workers. The percentage of workers who consulted a physician after receiving advice to do so did not differ by employment types, except in older men.ConclusionsIn Japan, workers with precarious employment, most notably hourly and dispatched workers, had a lower rate of health check‐ups compared with full‐time workers in permanent positions. Am. J. Ind. Med. 55:884–892, 2012. © 2012 Wiley Periodicals, Inc.
Carbon–Halogen Bond Formation by the Reductive Elimination of PdII Species
Authors: Jiang Xuefeng , Liu Hui , Gu Zhenhua 
Published: July 2012

AbstractIt is well known that Pd0 undergoes oxidative addition to organic halides, especially aryl or vinyl halides. In the contrast, the formation of organic halides by reductive elimination of RPdIIX (X=halogen) has been mostly ignored until very recently. This Focus Review discusses recent developments in palladium‐catalyzed carbon–halogen bond formation by the reductive elimination of RPdIIX. These new developments have enriched the scope of palladium‐catalyzed reactions, and provide a new way to construct carbon–halogen bonds.
Neubau der Kanalüberführung Elbeu in der Osthaltung des Mittellandkanals bei Magdeburg
Authors: Wiese Karl‐Heinz , Helfers Björn 
Published: July 2012

AbstractDer Mittellandkanal (MLK) ist eine Bundeswasserstraße und mit 325,3 km Länge die längste künstliche Wasserstraße in Deutschland. In europäischer Dimension ermöglicht der MLK über das innerdeutsche Kanalnetz eine Verbindung zwischen den Niederlanden, Belgien, Luxemburg, Frankreich und der Schweiz auf der einen, mit Polen und Tschechien auf der anderen Seite. Im Zuge des Ausbaus der West‐Ost‐verbindenden Binnenwasserstraßen (Projekt 17 der Verkehrsprojekte Deutsche Einheit) erfolgt derzeit der Neubau der Kanalüberführung bei Elbeu einschließlich des Ausbaus des Mittellandkanals von MLK‐km 315,15 bis 318,45. Mit einer eigens für die Maßnahme hergestellten Umfahrung des Kanals (Ausweiche) stellt dieses Projekt eine Besonderheit im Bereich der Infrastrukturplanung dar. Der Bericht beschreibt die Aufgaben und Anforderungen dieses herausragenden Projektes, welches sowohl bei der Planung als auch bei der Ausführung eine besondere Herausforderung für alle an der Umsetzung des Großprojektes Beteiligten darstellt.Reconstruction of the overfly Elbeu in the eastern section of the Mittellandkanal near MagdeburgThe Mittellandkanal (MLK) is a federal waterway and with a length of 325,3 kilometres the longest canal in Germany. Regarding Europe the MLK establishes together with the German canal network a connection among the Netherlands, Belgium, France and Switzerland on the one side and Poland and Czech Republic on the other side. In the course of expanding the east‐west connecting inland waterways (project No. 17 “Verkehrsprojekte Deutsche Einheit”) the new overfly Elbeu including the expansion of the Mittellandkanal from MLK‐km 315,15 to 318,45 is presently being built. Because of the bypass especially built for this construction work this represents a special project in infrastructure planning. The report shows the tasks and requirements of this outstanding project which represents as well in planning as in completion unique challenges for all parties involved.
Scientific basis for the Soviet and Russian radiofrequency standards for the general public
Authors: Repacholi Michael , Grigoriev Yuri , Buschmann Jochen , Pioli Claudio 
Published: July 2012

AbstractThe former Soviet Union (USSR) and the USA were the first countries to introduce standards limiting exposure to radiofrequency (RF) fields. However, the exposure limits in the USSR standards were always much lower than those in the USA and other countries. The objective of this article is to provide a history of the development of the Soviet and Russian RF standards. In addition, we summarize the scientific evidence used to develop the original USSR RF and subsequent Russian public health standards, as well as the mobile telecommunications standard published in 2003, but we do not critique them. We also describe the protective approaches used by the Soviet and Russian scientists for setting their limits. A translation of the papers of the key studies used to develop their standards is available in the online version of this publication. Bioelectromagnetics 33:623–633, 2012. © 2012 Wiley Periodicals, Inc.
Meggle Food Turm in Wasserburg
Authors: Fuchs Maximilian , Schmied Carola 
Published: July 2012

AbstractDer Neubau eines ca. 53 m hohen, turmartigen Produktionsgebäudes für die Lebensmittelindustrie in Wasserburg am Inn (Oberbayern) stellte aufgrund vielfältiger Anforderungen aus Bau und Nutzung eine spannende Ingenieuraufgabe für alle am Bau Beteiligten dar. Der vorliegende Beitrag beschreibt nach einer Darstellung der besonderen Randbedingungen aus Bauzeit, Bauablauf und späterer Nutzung den daraus resultierenden Entwurf, die Konstruktion und die Ausführung des Industriebauwerkes aus Stahlbeton.Meggle Food Tower in Wasserburg – Design and Construction of an industrial facility in reinforced concreteThe newly built 53 m high, tower‐like production building for the food industry company Meggle in Wasserburg am Inn (Oberbayern) was a challenging work for all participants due to requirements of construction and utilization. The paper in hand shows the construction and detailing of an industrial facility in reinforced concrete based on the special boundary conditions of construction progress, time schedule and subsequent utilization.