bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surfactant Protein A Enhances Production of Secretory Leukoprotease Inhibitor and Protects It from Cleavage by Matrix Metalloproteinases
Authors: Ramadas Ravisankar A. , Wu Lizhen , LeVine Ann Marie 
Published: April 2014

Abstract
Mice lacking surfactant protein A (SP-A) are susceptible to bacterial infection associated with an excessive inflammatory response in the lung. To determine mechanisms by which SP-A is antiinflammatory in the lung during bacterial infection, SP-A regulation of secretory leukoprotease inhibitor (SLPI), an inhibitor of serine proteases, was assessed. SLPI protein expression and antineutrophil elastase activity were reduced in bronchoalveolar fluid of SP-A−/− compared with SP-A+/+ mice. Intratracheal administration of SP-A to SP-A−/− mice enhanced SLPI protein expression and antineutrophil elastase activity in the lung. SLPI mRNA was similar in whole lung and alveolar type II cells; however, it was significantly reduced in alveolar macrophages from SP-A−/− compared with SP-A+/+ mice. In vitro, SP-A enhanced SLPI production by macrophage THP-1 cells but not respiratory epithelial A549 cells. SP-A inhibited LPS induced IκB-α degradation in THP-1 cells, which was partially reversed with knockdown of SLPI. Matrix metalloproteinase (MMP)-12 cleaved SLPI and incubation with SP-A reduced MMP-12-mediated SLPI cleavage. The collagen-like region of SP-A conferred protection of SLPI against MMP mediated cleavage. SP-A plays an important role in the lung during bacterial infection regulating protease and antiprotease activity.
The Adaptor Protein CIKS/Act1 Is Essential for IL-25-Mediated Allergic Airway Inflammation
Authors: Claudio Estefania , Sønder Søren Ulrik , Saret Sun , Carvalho Gabrielle , Ramalingam Thirumalai R. , Wynn Thomas A. , Chariot Alain , Garcia-Perganeda Antonio , Leonardi Antonio , Paun Andrea , Chen Amy , Ren Nina Y. , Wang Hongshan , Siebenlist Ulrich 
Published: April 2014

Abstract
IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well as in autoimmune diseases, such as rheumatoid arthritis and experimental autoimmune encephalomyelitis in animal models. IL-25 is a member of the IL-17 family of cytokines, but has been associated with Th2 responses instead and may negatively cross-regulate Th17/IL-17 responses. IL-25 can initiate an allergic asthma-like inflammation in the airways, which includes recruitment of eosinophils, mucus hypersecretion, Th2 cytokine production, and airways hyperreactivity. We demonstrate that these effects of IL-25 are entirely dependent on the adaptor protein CIKS (also known as Act1). Surprisingly, this adaptor is necessary to transmit IL-17 signals as well, despite the very distinct biologic responses that these two cytokines elicit. We identify CD11c+ macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo.
The Critical Role of Epithelial-Derived Act1 in IL-17- and IL-25-Mediated Pulmonary Inflammation
Authors: Swaidani Shadi , Bulek Katarzyna , Kang Zizhen , Liu Caini , Lu Yi , Yin Weiguo , Aronica Mark , Li Xiaoxia 
Published: April 2014

Abstract
IL-25 initiates, promotes, and augments Th2 immune responses. In this study, we report that Act1, a key component in IL-17-mediated signaling, is an essential signaling molecule for IL-25 signaling. Although Act1-deficient mice showed reduced expression of KC (CXCL1) and neutrophil recruitment to the airway compared with wild-type mice in response to IL-17 stimulation, Act1 deficiency abolished IL-25-induced expression of IL-4, IL-5, IL-13, eotaxin-1 (CCL11), and pulmonary eosinophilia. Using a mouse model of allergic pulmonary inflammation, we observed diminished Th2 responses and lung inflammation in Act1-deficient mice compared with wild-type mice. Importantly, Act1 deficiency in epithelial cells reduced the phenotype of allergic pulmonary inflammation due to loss of IL-17-induced neutrophilia and IL-25-induced eosinophilia, respectively. These results demonstrate the essential role of epithelial-derived Act1 in allergic pulmonary inflammation through the distinct impact of the IL-17R-Act1 and IL-25R-Act1 axes. Such findings are crucial for the understanding of pathobiology of atopic diseases, including allergic asthma, which identifies Act1 as a potential therapeutic target.
Myeloid-Specific Expression of Api6/AIM/Spα Induces Systemic Inflammation and Adenocarcinoma in the Lung
Authors: Qu Peng , Du Hong , Li Yuan , Yan Cong 
Published: April 2014

Abstract
To study the functional role of apoptosis inhibition of myeloid lineage cells in tumor formation, apoptosis inhibitor 6 (Api6/AIM/Spα) was overexpressed in a myeloid-specific c-fms-rtTA/(TetO)7-CMV-Api6 bitransgenic mouse model under the control of the c-fms promoter/intron 2. In this bitransgenic system, the Api6-Flag fusion protein was expressed in myeloid lineage cells after doxycycline treatment. Induction of Api6 abnormally elevated levels of macrophages, neutrophils, and dendritic cells in the bone marrow, blood, and lung in vivo. BrdU incorporation and annexin V binding studies showed systemically increased cell proliferation and inhibition of apoptosis in myeloid lineage cells. Api6 overexpression activated oncogenic signaling pathways, including Stat3, Erk1/2, and p38 in myeloid lineage cells in multiple organs of the bitransgenic mice. In the lung, severe inflammation and massive tissue remodeling were observed in association with increased expression of procancer cytokines/chemokines, decreased expression of proapoptosis molecule genes, and increased expression of matrix metalloproteinase genes as a result of Api6 overexpression. Oncogenic CD11b+/Gr-1+ myeloid-derived suppressor cells were systemically increased. After Api6 overexpression, lung adenocarcinoma was observed in bitransgenic mice with a 35% incidence rate. These studies suggest that dysregulation of myeloid cell populations by extracellular Api6 signaling leads to abnormal myelopoiesis and lung cancer.
A Single Helper T Cell Clone Is Sufficient to Commit Polyclonal Naive B Cells to Produce Pathogenic IgG in Experimental Pemphigus Vulgaris
Authors: Takahashi Hayato , Kuwana Masataka , Amagai Masayuki 
Published: April 2014

Abstract
The development of naive B cells into IgG-producing memory B cells requires cognate T cell-B cell interaction in Ag-specific immune responses. It is unknown whether a single T cell clone is sufficient or whether multiple clones are necessary to induce polyclonal IgG production in vivo. We addressed this issue using a mouse model of pemphigus vulgaris, a fatal autoimmune blistering skin disease caused by IgG autoantibodies against desmoglein (Dsg) 3. We previously isolated several Dsg3-reactive T cell clones from Dsg3−/− mice. Among these, two pathogenic T cell clones induced anti-Dsg3 IgG production and the development of a pemphigus phenotype when adoptively transferred with unprimed B cells from Dsg3−/− mice. IgG Abs harvested from recipient mice reacted with at least three parts of the extracellular domain of Dsg3, as determined using domain-swapped Dsg3/Dsg1 molecules. The anti-Dsg3 IgGs included at least two subclasses among IgG1, IgG2a, IgG2b, and IgG3 in each mouse. The anti-Dsg3 IgG induced by Dsg3-reactive T cell clones with primed B cells from Dsg3−/− mice also showed reactivity against different parts of the molecule, with a similar epitope distribution. Together, these results indicate that a single potent Dsg3-reactive T cell is sufficient to commit polyclonal naive B cells to produce pathogenic anti-Dsg3 IgG Abs and induce the PV phenotype. These findings provide an important framework for examining immunological mechanisms in Ab-mediated autoimmune diseases.
Kijken en bekeken worden - De avonden als stripverhaal
Authors: Hermann Christine 
Published: April 2014

‘Comic version offers new insights’ – with these words the Stichting Beeldverhaal Nederland acclaimed the publication of Dick Matena’s comic version of De avonden, incorporating the complete text of the novel. But what actually is the benefit of Matena’s approach? In this paper I will investigate how the comic artist has translated Reve’s style into images, paying special attention to visual focalisation techniques. Several examples shall illustrate by which techniques certain themes (monotony, isolation, repressed sexuality) are evoked without being actually depicted. What the text leaves unsaid, is evoked on the panels by means of e.g. layout, colouring, pictorial composition, camera angle, field size, absence of mimicry and (physical as well as eye) contact.
There is, however, one theme which is indeed depicted, namely vision. Whereas the novel can only describe observation, in the comic it can be actually shown. The reader is at the same time a viewer: he watches the protagonist and at the same time literally shares his view. In this way the viewer gets himself involved in the story and thus in a way satisfies the desire of the protagonist to be ‘seen’. The images thus not only repeat or supplement the message of the text, but also provide an additional semantic value.
Porcine Skeletal Muscle-Derived Multipotent PW1pos/Pax7neg Interstitial Cells: Isolation, Characterization, and Long-Term Culture
Authors: Lewis Fiona C. , Henning Beverley J. , Marazzi Giovanna , Sassoon David , Ellison Georgina M. , Nadal-Ginard Bernardo 
Published: April 2014

Abstract

Developing effective strategies for the regeneration of solid tissue requires an understanding of the biology underlying the tissue's endogenous repair mechanisms. PW1/Peg3pos/Pax7neg skeletal muscle-derived interstitial progenitor cells (PICs) were first identified recently in the interstitium of murine skeletal muscle and shown to contribute to muscle fiber regeneration in vivo. PICs, therefore, represent a novel candidate resident progenitor cell for muscle regeneration. To explore the potential of these cells for clinical translation, we must ascertain the presence of PICs in larger mammalian species and identify criteria to successfully isolate and expand this population. In this study, we report the isolation, characterization, and maintenance of multipotent PICs from juvenile porcine skeletal muscle. We show that porcine PICs can be reproducibly isolated from skeletal muscle, express stem/progenitor cell markers, and have a stable phenotype and karyotype through multiple passages. Furthermore, porcine PICs are clonogenic and multipotent, giving rise to skeletal myoblast/myotubes, smooth muscle, and endothelial cells. In addition, PICs can be induced to differentiate into cardiomyocyte-like cells. These results demonstrate, in an animal model with size and physiology extrapolatable to the human, that porcine skeletal muscle-derived PW1pos/Pax7neg PICs are a source of stem/progenitor cells. These findings open new avenues for a variety of solid tissue engineering and regeneration using a single multipotent stem cell type isolated from an easily accessible source, such as skeletal muscle.
Palladium on Carbon‐Catalyzed One‐Pot N‐Arylindole Synthesis: Intramolecular Aromatic Amination, Aromatization, and Intermolecular Aromatic Amination
Authors: Monguchi Yasunari , Marumoto Takahisa , Takamatsu Haruki , Sawama Yoshinari , Sajiki Hironao 
Published: April 2014

AbstractIndole and indoline derivatives were selectively and temperature dependently synthesized via the intramolecular cross‐coupling reaction between the amino and aromatic bromine functionalities of 2‐bromophenethylamine derivatives in the presence of 10% palladium on carbon (Pd/C), 1,1′‐bis(diphenylphosphino)ferrocene (DPPF), and sodium tert‐butoxide (NaO‐t‐Bu) in mesitylene at 140 and 200 °C, respectively. The neutralization using acetic acid after formation of the indoline derivatives effectively promoted their aromatization, and the corresponding indole derivatives were obtained at 140 °C. Furthermore, various aryl groups were also introduced to the N‐1 position of the indole, pyrrole, and carbazole rings by their direct intramolecular arylation with aryl halides and a one‐pot protocol for N‐arylindole synthesis from 2‐bromophenethylamine was developed.magnified image
DNA Nanoflowers for Multiplexed Cellular Imaging and Traceable Targeted Drug Delivery
Authors: Hu Rong , Zhang Xiaobing , Zhao Zilong , Zhu Guizhi , Chen Tao , Fu Ting , Tan Weihong 
Published: April 2014

AbstractWe present a facile approach to make aptamer‐conjugated FRET (fluorescent resonance energy transfer) nanoflowers (NFs) through rolling circle replication for multiplexed cellular imaging and traceable targeted drug delivery. The NFs can exhibit multi‐fluorescence emissions by a single‐wavelength excitation as a result of the DNA matrix covalently incorporated with three dye molecules able to perform FRET. Compared with the conventional DNA nanostructure assembly, NF assembly is independent of template sequences, avoiding the otherwise complicated design of DNA building blocks assembled into nanostructures by base‐pairing. The NFs were uniform and exhibited high fluorescence intensity and excellent photostability. Combined with the ability of traceable targeted drug delivery, these colorful DNA NFs provide a novel system for applications in multiplex fluorescent cellular imaging, effective screening of drugs, and therapeutic protocol development.
A Biomimetic Catalytic Aerobic Functionalization of Phenols
Authors: Esguerra Kenneth Virgel N. , Fall Yacoub , Lumb Jean‐Philip 
Published: April 2014

AbstractThe importance of aromatic CO, CN, and CS bonds necessitates increasingly efficient strategies for their formation. Herein, we report a biomimetic approach that converts phenolic CH bonds into CO, CN, and CS bonds at the sole expense of reducing dioxygen (O2) to water (H2O). Our method hinges on a regio‐ and chemoselective copper‐catalyzed aerobic oxygenation to provide ortho‐quinones. ortho‐Quinones are versatile intermediates, whose direct catalytic aerobic synthesis from phenols enables a mild and efficient means of synthesizing polyfunctional aromatic rings.
Dermal Developmental Toxicity of N‐Phenylimide Herbicides in Rats
Authors: Kawamura Satoshi , Kato Terushige , Nakaoka Masanao , Fantel Alan G. 
Published: April 2014

BackgroundS‐53482 and S‐23121 are N‐phenylimide herbicides and produced embryolethality, teratogenicity (mainly ventricular septal defects and wavy ribs), and growth retardation in rats in conventional oral developmental toxicity studies. Our objective in this study was to investigate whether the compounds induce developmental toxicity via the dermal route, which is more relevant to occupational exposure, hence better addressing human health risks.MethodsS‐53482 was administered dermally to rats at 30, 100, and 300 mg/kg during organogenesis, and S‐23121 was administered at 200, 400, and 800 mg/kg (the maximum applicable dose level). Fetuses were obtained by a Cesarean section and examined for external, visceral, and skeletal alterations.ResultsDermal exposure of rats to S‐53482 at 300 mg/kg produced patterns of developmental toxicity similar to those resulting from oral exposure. Toxicity included embryolethality, teratogenicity, and growth retardation. Dermal administration of S‐23121 at 800 mg/kg resulted in an increased incidence of embryonic death and ventricular septal defect, but retarded fetal growth was not observed as it was following oral exposure to S‐23121.ConclusionsBased on the results, S‐53482 and S‐23121 were teratogenic when administered dermally to pregnant rats as were the compounds administered orally. Thus, investigation of the mechanism and its human relevancy become more important.
Effects of Macrolide Antibiotics on Rat Embryonic Heart Function In Vitro
Authors: Nilsson Mats F. , Webster William S. 
Published: April 2014

The Swedish Medical Product Agency (MPA) has listed erythromycin as a suggested human teratogen, causing cardiovascular malformations. It is further suggested that this may be a class effect of macrolide antibiotics. The proposed teratogenic mechanism is blockade of the human ether‐á‐go‐go‐related (hERG)/IKr current in the embryonic heart causing bradycardia and arrhythmia resulting in altered cardiac blood flow and/or embryonic hypoxia. To test this hypothesis, we examined the effect of three macrolide antibiotics on the function of the rat embryonic heart. Gestational day 13 rat embryos in vitro were exposed to erythromycin (25–500 μM), clarithromycin (25–500 μM), or azithromycin (100 μM to 1 mM) for 3 hr. The effect on the embryonic heart was monitored every hour. The results showed that erythromycin and clarithromycin caused a concentration‐dependent bradycardia. Twenty‐five micromolar was a no‐effect concentration for erythromycin and was close to a no‐effect concentration for clarithromycin. Azithromycin only caused significant bradycardia at 1 mM. Additional studies were performed with the embryos cultured at 40°C instead of 38°C, to mimic fever. The increased temperature increased the number of arrhythmias but did not worsen the drug‐induced bradycardia. The results support the concept that erythromycin and clarithromycin can adversely affect the embryonic heart but only at concentrations well outside expected embryonic exposure in the human
Valve‐in‐valve implantation of a novel and small self‐expandable transcatheter heart valve in degenerated small surgical bioprostheses: The Hamburg experience
Authors: Diemert Patrick , Seiffert Moritz , Frerker Christian , Thielsen Thomas , Kreidel Felix , Bader Ralf , Schirmer Johannes , Conradi Lenard , Koschyk Dietmar , Schnabel Renate , Reichenspurner Hermann , Blankenberg Stefan , Kuck Karl‐Heinz , Treede Hendrik , Schaefer Ulrich 
Published: April 2014

BackgroundTranscatheter valve‐in‐valve (VIV) implantation has emerged as a novel treatment option in patients with degenerated aortic bioprostheses and high surgical risk. However, VIV implantation in small aortic bioprostheses using first generation TAVI devices has frequently resulted in high postprocedural gradients and small effective orifice areas. Recently, an updated version of the self‐expandable Medtronic CoreValve prosthesis, which is particularly suitable for small aortic annuli, has become available. We report on the feasibility and early results of VIV implantation using this novel device in a series of patients with degenerated small aortic bioprostheses.Methods and Results16 patients from two Hamburg hospitals (age range 72–92 years) underwent implantation of a 23‐mm CoreValve Evolut (Medtronic, Minneapolis, MN, USA) transcatheter heart valve into failing aortic bioprostheses with internal diameters below 21 mm. All patients were considered high risk for surgical aortic valve replacement after evaluation by an interdisciplinary heart team mean (logistic EuroSCORE range 9.0–88%). Implantation was successful without relevant remaining aortic regurgitation or signs of stenosis and a marked reduction in postprocedural gradientswas observed in 14 out of 16 patients. The mean gradient was reduced from from 34 mm Hg (SEM 10 mm Hg) to 14 mm Hg (SEM 6 mm Hg). No major device‐ or procedure‐related adverse events occurred during 30‐day follow up and clinical improvement was observed.ConclusionsFailing aortic bioprostheses with small internal diameters continue to be a challenging pathology for TAVI due to the risk of high residual gradients and small aortic orifice areas. This report provides first evidence that the 23‐mm CoreValve Evolut, a novel self‐expanding prosthesis, provides an improved treatment option in these specific patients due to its low profile which resulted in promising early results. © 2013 Wiley Periodicals, Inc.
Classical Hodgkin Lymphoma involving the central nervous system (brain) – an unusual presentation
Authors: van Blydenstein Sarah Alexandra , Patel Moosa , Philip Vinitha , Lakha Atul , Pather Sugeshnee , Westgarth‐Taylor Tracy , Thompson Eddison , Kolloori Avinash 
Published: April 2014

Key Clinical MessageIntracranial Hodgkin lymphoma (HL) is considered so atypical that an intracranial space‐occupying lesion in a patient with known HL should be thoroughly investigated to rule out a second disease process.
From the Lindlar Catalyst to Supported Ligand‐Modified Palladium Nanoparticles: Selectivity Patterns and Accessibility Constraints in the Continuous‐Flow Three‐Phase Hydrogenation of Acetylenic Compounds
Authors: Vilé Gianvito , Almora‐Barrios Neyvis , Mitchell Sharon , López Núria , Pérez‐Ramírez Javier 
Published: April 2014

AbstractSite modification and isolation through selective poisoning comprise an effective strategy to enhance the selectivity of palladium catalysts in the partial hydrogenation of triple bonds in acetylenic compounds. The recent emergence of supported hybrid materials matching the stereo‐ and chemoselectivity of the classical Lindlar catalyst holds promise to revolutionize palladium‐catalyzed hydrogenations, and will benefit from an in‐depth understanding of these new materials. In this work, we compare the performance of bare, lead‐poisoned, and ligand‐modified palladium catalysts in the hydrogenation of diverse alkynes. Catalytic tests, conducted in a continuous‐flow three‐phase reactor, coupled with theoretical calculations and characterization methods, enable elucidation of the structural origins of the observed selectivity patterns. Distinctions in the catalytic performance are correlated with the relative accessibility of the active site to the organic substrate, and with the adsorption configuration and strength, depending on the ensemble size and surface potentials. This explains the role of the ligand in the colloidally prepared catalysts in promoting superior performance in the hydrogenation of terminal and internal alkynes, and short‐chain alkynols. In contrast, the greater accessibility of the active surface of the Pd–Pb alloy and the absence of polar groups are shown to be favorable in the conversion of alkynes containing long aliphatic chains and/or ketone groups. These findings provide detailed insights for the advanced design of supported nanostructured catalysts.